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Mineralization of Bones and Teeth
Abstract
Bones and teeth consist of an inorganic calcium phosphate mineral approximated by hydroxylapatite and matrix proteins. The physical and chemical properties of these "bioapatite" crystals are different from those of geologic hydroxylapatite because of the way they are formed, and these unique properties are required for fulfilling the biological functions of bones and teeth. Recent biochemical studies provide insight into the factors controlling the formation and growth of bioapatite crystals and how alteration in the mineralization process can lead to diseases such as osteoporosis. New spectroscopic and microscopic techniques are enabling scientists to characterize changes in crystal properties in these diseases, providing potentially fruitful areas of collaboration among geochemists, mineralogists, and biological researchers and offering hope for the development of novel therapies.
... These results are consistent with previous findings on the crystallization of 1d glass around 800 °C [28]. All three crystalline phases are highly biocompatible and suitable for being applied in bone repair surgery as fluorapatite occurs naturally in the mixed bio-apatites that form the mineral phase of bones and teeth in mammals [29]; wollastonite has been well known as an osseous substitute since the 1980s, when Kokubo's team developed the first machinable apatite/wollastonite bioactive glass-ceramics [30]; and diopside was more recently claimed to be superior to other silicate bioceramics due to its better mechanical properties, slower dissolution rate, improved apatite-forming ability, and excellent in vivo biocompatibility [31]. The XRD pattern shown in Figure 3a exhibits the typical broad halo (also called an "amorphous halo") of silicate glasses (2θ range of 25 to 38 • ) without any diffraction peaks, thus confirming that the as-quenched material is actually in the glassy state. ...
... These results are consistent with previous findings on the crystallization of 1d glass around 800 • C [28]. All three crystalline phases are highly biocompatible and suitable for being applied in bone repair surgery as fluorapatite occurs naturally in the mixed bio-apatites that form the mineral phase of bones and teeth in mammals [29]; wollastonite has been well known as an osseous substitute since the 1980s, when Kokubo's team developed the first machinable apatite/wollastonite bioactive glass-ceramics [30]; and diopside was more recently claimed to be superior to other silicate bioceramics due to its better mechanical properties, slower dissolution rate, improved apatite-forming ability, and excellent in vivo biocompatibility [31]. ...
... These results are consistent with previous findings on the crystallization of 1d glass around 800 °C [28]. All three crystalline phases are highly biocompatible and suitable for being applied in bone repair surgery as fluorapatite occurs naturally in the mixed bio-apatites that form the mineral phase of bones and teeth in mammals [29]; wollastonite has been well known as an osseous substitute since the 1980s, when Kokubo's team developed the first machinable apatite/wollastonite bioactive glass-ceramics [30]; and diopside was more recently claimed to be superior to other silicate bioceramics due to its better mechanical properties, slower dissolution rate, improved apatite-forming ability, and excellent in vivo biocompatibility [31]. The multiphase glass-ceramic material obtained by sinter-crystallization of 1d glass has the benefit of synergistically combining the regenerative effects of the different phases; this aspect deserves further research. ...
Implantation of three-dimensional (3D) bioactive glass-derived porous scaffolds is an effective strategy for promoting bone repair and regeneration in large osseous defect sites. The present study intends to expand the potential of a SiO2–P2O5–CaO–MgO–Na2O–CaF2 glass composition, which has already proven to be successful in regenerating bone in both animals and human patients. Specifically, this research work reports the fabrication of macroporous glass–ceramic scaffolds by the foam replica method, using the abovementioned bioactive glass powders as a parent material. The sinter-crystallization of the glass powder was investigated by hot-stage microscopy, differential thermal analysis, and X-ray diffraction. Scanning electron microscopy was used to investigate the pore–strut architecture of the resultant glass–ceramic scaffolds in which diopside, fluorapatite, and wollastonite crystallized during thermal treatment. Immersion studies in simulated body fluids revealed that the scaffolds have bioactive behavior in vitro; the mechanical properties were also potentially suitable to suggest use in load-bearing bone applications.
... Bones and teeth are composite structures consisting mostly of a collagenous organic matrix mineralized with a hydroxylapatite analog [1]. Bone and dentin are produced by osteoblasts and odontoblasts, respectively, whose main function is to form a mineralized matrix by secreting collagenous and noncollagenous proteins, as well as mediators of mineralization [2]. ...
... Most high BMD and/or high bone mass phenotypes reflect impaired resorption by dysfunctional osteoclasts, which result in osteopetrosis or pycnodysostosis [1]. Mutations in any of the many different genes responsible for osteoclast differentiation and function can result in high bone mass phenotypes in mice. ...
... Renal osteodystrophy associated with chronic kidney disease is also characterized by low BMD due to increased osteoclasia (Figure 23.3) and medial arterial calcification [85,86]. Any disruption in the balance between bone resorption and formation can lead to reduced trabecular and cortical bone mass, which in turn increases bone fragility and fracture susceptibility [1]. ...
Bones and teeth are composite structures consisting mostly of a collagenous organic matrix mineralized with a hydroxylapatite analog. Pathologists should evaluate bones and teeth together because many bone abnormalities are accompanied by dentin defects in teeth. Adult bone can be divided into two types: cortical bone, and trabecular bone. Histomorphometry of bone and cartilage is an important tool with which to study the pathophysiology of bone disease in mice. DXA is the most commonly used method for high throughput screening of genetically engineered mouse to quickly identify lines with bone mineral content phenotypes. Biomineralization processes in bones and teeth involve complex, tightly regulated interactions between promoters and inhibitors of mineralization. Studies on the epitheliomesenchymal interactions in mouse incisors have proven particularly useful in elucidating many of the molecular pathways and morphogenetic processes involved in tooth development and the pathogenesis of dental diseases.
... Bones can be divided into cancellous and compact types, composed of water (approximately 10%) and closely linked organic (approximately 25%) and inorganic phases (approximately 60-70%). The former is mainly represented by lipids and proteins, 90% of which are type I collagen, formed by amino acid chains in a triple-helical structure [4,5]. Collagen molecules in the bone form elastic fibrils, held together by hydrogen bonds [6]. ...
... Collagen molecules in the bone form elastic fibrils, held together by hydrogen bonds [6]. In the empty spaces between collagen molecules and fibrils are inorganic plate-shaped nanocrystals of non-stoichiometric (highly disordered) apatite with predominantly carbonate (3-8%) but also other (e.g., Na, Mg, Al, Pb, HPO 4 ) substitutions replacing phosphates and hydroxy groups [5,[7][8][9][10][11][12][13]. Furthermore, bone mineral is hydrated as it contains water in its structure [14]. ...
Charred and burned human and animal skeletal remains are frequently found in archaeological records and can also be subjects of forensic investigations. Heat exposure causes specific changes to the physical and chemical characteristics of these remains, offering valuable insights into their taphonomic history. This research combines the commonly used ATR-FTIR (Attenuated Total Reflectance–Fourier Transform Infrared) spectroscopy with the rarely utilised density measurements obtained from Multidetector CT (Computed Tomography) to investigate changes in defleshed bovine cortical bone exposed to different temperatures for varying durations. The inclusion of density measurements is significant because Multidetector CT analysis is non-destructive and can be valuable when remains cannot be removed from their burial context (e.g., urn) or cannot be damaged. The results indicate complex changes in both organic and inorganic components, affecting crystallinity and density. Lower temperatures primarily affect organic matter, while higher temperatures induce significant changes in the mineral lattice and phase transitions. The transformation from β-tricalcium phosphate to α-tricalcium phosphate at high temperatures likely impacts the bone’s crystallinity and density. Bone density measured by CT scans provided additional information that complemented the interpretations of FTIR spectroscopy. While CT scans offer important data for planning non-destructive analyses of remains, they present only one layer of information. Therefore, CT scans need to be combined with other techniques to provide comprehensive interpretations of the changes occurring in the bone. Further research is needed on density measurements and other potentially non-destructive analyses to fully unlock the potential of Multidetector CT analyses.
... The dynamics of formation and transformation of the phosphates of calcium (CaP) are important in vertebrates. CaP is significant in hard tissues such as teeth and bones [1][2][3]. Various CaP phases precipitated in aqueous solutions and also probably in vivo mainly include amorphous calcium phosphate (Ca x H y (PO 4 ) z ⋅H 2 O, ACP), calcium phosphate dehydrate (CaHPO 4 ⋅H 2 O, DCPD), octacalcium phosphate (Ca 8 (H-PO 4 ) 2 (PO 4 ) 4 .5 H 2 O, OCP), and hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 , HA) [4,5]. ...
... Biomimetic mineralization in complex organic hydrogels has three steps: (1) Initiation of the nucleation of the minerals leading to intermediate amorphous phases followed by (2) aggregation and the stabilization of intermediate phases and (3) final deposition of crystalline products during the biomineralization [22][23][24]. As the initial phase of the biomineral formed in vivo is liquid-like, anisotropic, and facilitated by the polymer-like domain on the protein, it is called the polymer-induced liquid precursor (PILP) phase [25,26]. ...
... Calcium (Ca) is a critical alkaline earth metal that is the most abundant inorganic nutrient in the body, playing a key role in the formation and maintenance of bones and teeth [1]. Nearly 99% of the body's total Ca is stored in bones and teeth, where it is incorporated into hydroxylapatite (HAp; Ca 10 (PO 4 ) 6 (OH) 2 ) and matrix proteins [1][2][3]. ...
... Calcium (Ca) is a critical alkaline earth metal that is the most abundant inorganic nutrient in the body, playing a key role in the formation and maintenance of bones and teeth [1]. Nearly 99% of the body's total Ca is stored in bones and teeth, where it is incorporated into hydroxylapatite (HAp; Ca 10 (PO 4 ) 6 (OH) 2 ) and matrix proteins [1][2][3]. Despite being present in lower concentrations in blood and soft tissues, Ca also plays a crucial role in several physiological processes, including muscle contraction, signal transmission, cell apoptosis, cell reproduction, and blood coagulation [4,5]. It is important to maintain narrow blood Ca levels, as higher concentrations can be toxic to cells. ...
Potassium (K) is an essential electrolyte for cellular functions in living organisms, and disturbances in K+ homeostasis could lead to various chronic diseases (e.g. hypertension, cardiac disease, diabetes, and bone health). However, little is known about the natural distribution of stable K isotopes in mammals and its application to investigate the bodily homeostasis and/or as a biomarker for diseases. Here, we measured K isotopic compositions (δ41K, per mil deviation of 41K/39K from the NIST SRM 3141a standard) of brain, liver, kidney, and red blood cells (RBCs) from 10 mice (five females and five males) with three different genetic backgrounds. Our results reveal that different organs and RBCs have distinct K isotopic signatures. Specifically, the RBCs have heavy K isotopes enrichment with δ41K ranging from 0.67 to 0.08 ‰, while the brains show lighter K isotopic compositions with δ41K ranging from -1.13 to -0.09 ‰ compared to the livers (δ41K = -0.12 ± 0.58 ‰) and kidneys (δ41K = -0.24 ± 0.57 ‰). We found that the K isotopic and concentration variability is mostly controlled by the organs, with a minor effect of the genetic background and sex. Our study suggest that the K isotopic composition could be used as a biomarker for changes in K+ homeostasis and related diseases such as hypertension, cardiovascular, and neurodegenerative diseases.
... (1) ray-Darling basin) [45] ，同时考虑地理位置，本文也比较 Hf/ (mg·kg −1 ) 0 Mid-ocean ridge basalt data refer to reference [54]; Australian wind-dust sediment data refer to reference [55]; pore water data refer to reference [56]; seawater data refer to reference [57]; hydrothermal data refer to reference [58]; NASC data refer to reference [37] 成岩微结核的REY，比较了NASC标准化配分模式 (图14 Picture on a refer to reference [72], the dotted present the mixing trends between two genetic processes highlighting the continuum existing between hydrogenetic-hydrothermal crusts and hydrogenetic-diagenetic nodules, solid arrows show evolution trends of a sample set related to only one genetic process without influence of another one; picture on b refer to reference [73] La ...
... The range of CaO/P 2 O 5 in fish teeth (1.30−1.90) refer to reference [53], and the DSDP and ODP site data refer to references [24-25] La Ce Pr Nd Sm Eu Gd Tb Dy Y Ho Er Tm Yb Lu La Ce Pr Nd Sm Eu Gd Tb Dy Y Ho Er Tm Yb Lu La Ce Pr Nd Sm Eu Gd Tb Dy Y Ho Er Tm North American shale standardized-normalized rare earth elements patterns for different materials 洋中脊玄武岩数据参考文献[54]；澳大利亚风尘沉积物数据参考文献[55]；孔隙水数据参考文献[56]；海水数据参考文献[57]； 热液数据参考文献[58]；北美页岩标准化数据参考文献[37] ...
In this paper, sediment smear observations, X-ray diffraction analyses, major, trace and rare earth elements
analyses, and in situ micro zone geochemical analyses of single minerals were carried out on samples of core
GC02 and GC06 from the rare earth-rich deep-sea sediments in the Central Indian Ocean Basin to explore their geochemical
characteristics, material sources and enrichment mechanisms of rare earth elements (REY). The results
show that the sediment types of core GC02 are calcareous clay and zeolitic clay, and the sediment types of core
GC06 are calcareous clay, zeolite-bearing clay and zeolitic clay. Rare earth elements are enriched in zeolite-bearing
clays and zeolitic clays. The North American Shale Composite (NASC) Standardized patterns of REY in the
sediments indicate a possible seawater origin. Mineralogical and geochemical signatures indicate that the terrestrial
fraction of these sediments in the study area should be the eolian dust material originated primarily from Australian.
Elemental correlations and CaO/P2O5 ratios indicate that the main host mineral of REY in REY-rich deep-sea sediments
is bioapatite (fish teeth/bone), followed by Fe-Mn micronodule. This study summarizes and discusses the
formation mechanism of REY-rich sediments and improves a conceptual model for the formation process of REY-
rich sediments.
... It protects internal organs and is a site of muscle attachment. The principal mineral components of bone are calcium (Ca) and phosphorus (P) which precipitate as apatite (Ca10(PO4)6(OH)2) (Boskey, 2007) within an organic matrix mainly consisting of type I collagen (Young, 2003). Bone acts as a mineral storage (Lall, 2002;Lall and Lewis-McCrea, 2007;Tarlo, 1964) and has endocrine and metabolic functions (Confavreux et al., 2009;. ...
... Although teleost fishes can effectively cope with high CO2 (hypercapnia), studies show that freshwater and seawater Atlantic salmon (Salmo salar, L.) reared in high CO2 suffer a reduced growth and reduced feed conversion ratio (Eddy et al., 1977;Fivelstad et al., 1998;1999;2003;2007;2018;Gil-Martens et al., 2006). High water CO2 increases plasma pH (Fivelstad et al., 2003;Mota et al., 2019) as a compensatory response of the organism to the systemic acidosis. ...
Summary
Skeletal deformities in farmed Atlantic salmon (Salmo salar, L.) and other farmed teleost fish raise concern about animal welfare. Severe vertebral deformities reduce animal growth rate and overall skeletal health. In aquaculture, this leads to product quality degradation. One of the most commonly discussed factors that influences skeletal health is dietary phosphorus (P). Dietary P is essential for a proper mineralisation of the skeleton. To prevent deformity development in Atlantic salmon it is currently common practice to add P in the diet in a higher amount than required. Still, P supplementation in the feed for farmed fish requires appropriate management. An excess of dietary P increases the dietary P to calcium ratio, which reduced zinc absorption, a trace element involved in immunity, growth and mineralisation. Zinc is the central atom of alkaline phosphatase which removes pyrophosphate, a potent bone mineralisation inhibitor. High dietary P increases animal P excretion. The resulting P discharge from fish farms can lead to environmental pollution. Importantly, the source of dietary P is non-renewable which further emphasises the need for its responsible use. Another factor possibly affecting skeletal health is elevated CO2 level in the water, a common and unwanted consequence of increased rearing densities and recirculating systems used in aquaculture. Like a deficiency of dietary P, high levels of CO2 have been previously suggested as a factor inducing skeletal deformities in Atlantic salmon.
The research within the frame of this PhD thesis aims to test (i) the effect of low and high levels of dietary P fed to farmed Atlantic salmon in freshwater on bone formation and mineralisation in the vertebral column, and the recovery from low and high dietary P feeding in seawater Atlantic salmon, and (ii) the synergistic effect of low or high dietary P and carbon dioxide (CO2) injected into the environment on Atlantic salmon post-smolts.
The aims outlined above are addressed in three chapters, following an introductory chapter that outlines the fundamentals of skeleton development, vertebral deformities, P metabolism, life cycle, and distribution of Atlantic salmon, and its relation to aquaculture.
Chapter II analyses the results of a mono-factorial study (spanning 11 weeks) on the impact of feeding low or high levels of dietary P on the structure of the vertebral bodies in the freshwater parr stage of Atlantic salmon. This study revealed the presence of a background level of mild vertebral deformities in all groups, irrespective of dietary P. Low dietary P did not increase vertebral deformities. Surprisingly, growth of low P animals, was comparable with regular P and high P animals, a finding discussed in terms of continuous feeding as a partial compensation for low dietary P. In low P conditions, bone formation continues but bone mineralisation is arrested discontinues, leading to the development of extended areas of non-mineralised bone (osteomalacia). The total Ca and P content in the vertebrae and opercula is reduced by about 50% in low P compared to regular and high P animals. In line with the reduced mineral content, vertebral centra stiffness is also reduced in low P animals. While the structural and functional integrity of the vertebral bodies in low P animals is maintained, animals show minor morphological alterations of the vertebral bodies. Low P animals develop a slight inward bending of the vertebral body endplates, intervertebral joints acquire an increased length and thickness, and ectopic cartilage develops at the interface between the vertebral body endplates and bone trabeculae. Importantly, this study provides supporting evidence that high dietary P does not benefit bone mineralisation and bone health compared with a regular dietary P. Regular and high P animals show a comparable extension of the osteoid (non-mineralised bone). Both groups have similar bone and opercula mineral content and vertebral centra stiffness.
Chapter III assesses if and how vertebral centra deformities develop over the course of 69 weeks. A total of 135 Atlantic salmon fed a low or high P in freshwater, followed by a regular diet prior to smoltification were PIT-tagged and subjected to long-term monitoring by means of x-ray imaging at three time points: prior to smoltification (50 g), at seawater stage (700 g), and at harvest (4.5 kg).
Four categories of vertebral deformity development can be identified: (1) recovery, (2) containment, (3) progression, and (4) late-onset. Deformities with a negative impact on the vertebral centra but with intact intervertebral joints can fully recover in seawater. Recovered deformities include both those following a low P diet history (low-mineralised and hyper-dense vertebrae), and deformities independent of the diet P history (mildly compressed and vertically shifted vertebrae). Stable vertebral fusions which affect two to three vertebral centra and the intervertebral spaces can be contained. Progressive vertebral fusions affect more than three vertebral centra and intervertebral spaces and worsen over time. Notably, this type of severe vertebral deformity can be observed as early as in freshwater stages. Vertical shifts, fusions, and compressions are also found to develop in late seawater stages of Atlantic salmon (late-onset deformities). The dietary P history was found not to be associated with contained, progressive, or late-onset deformities. This provides further evidence that low dietary P is not the main factor for the development of deformities in Atlantic salmon. The above analysis is important in the context of farming. Early detection of animals susceptible to develop severe deformities can prevent rearing of individuals with compromised bone health.
Chapter IV discusses the observed effect of elevated CO2 level on increased bone mineralisation under low P diet condition, which offers the possibility to reduce the P content in commercial salmon feeds. It complements studies on the effect of high dietary P on bone health in seawater stages of Atlantic salmon. Both high P and high CO2 result in a reduced feed intake and growth of the animals. Increased bone and scale mineralisation in animals reared in high CO2 water is only observed when the dietary P is low. The osteoblasts and osteocytes in low P animals are observed to downregulate the synthesis of fgf23, a hormone responsible for inhibition of renal phosphate reabsorption. It is hypothesised that in low P animals not only renal phosphate reabsorption but also intestinal phosphate absorption is increased. These findings provide the first insights on how to implement a reduction of dietary P use under high CO2 water conditions without jeopardizing bone mineralisation, an application which nevertheless requires further research and elaboration. To conclude, the hypothesis that high levels of dietary P are required to reduce the risk of vertebral deformities and to secure healthy bone formation and mineralisation must be rejected. Likewise, the hypothesis that high levels of CO2 are detrimental for the skeletal health of seawater stage Atlantic salmon is refuted by the observation that high CO2 levels in water increased bone mineralisation in animals fed a low P diet, a condition which leads to formation of non-mineralised bone.
Chapter V evaluates the use of low and high dietary P in the feeds for farmed Atlantic salmon. It discusses the increased mechanical load exerted by the axial musculature during handling stress as a potential factor inducing the development of vertebral deformities. A possibility to predict the prevalence and severity of vertebral deformities in the freshwater stages of Atlantic salmon to improve animal welfare in seawater is elaborated. Future prospects discuss the potential to reduce dietary P in aquaculture systems with a high level of CO2 and improved utilisation of P under regimes which involve periods of low dietary P feeding. This section furthermore considers alternative products to wild caught fishmeal and fish oil based products. These include insect meal, genetically modified terrestrial plants producing omega-3 long chain polyunsaturated fatty acids, and an increase in P availability with the application of phytase in a commonly used plant-based product.
... The characteristic of Turf water characteristic are high color intensity (brownish red), low pH, high content of organic material, turbidity and the low content of suspended particle and low cation, 4 the low pH in turf water can induce tooth damages such as dissolving tooth enamel so that the tooth becomes porous quickly and causes demineralization as well as erosion in the tooth. 3, 5 Mouth cavity contents various colonies of bacteria. These microflorae are normally found on the surface of mouth cavity. ...
... Saliva acidity (pH) in lower level is optimal for bacteria to grow up, bacteria will grow up well. 5 The increase of bacterial quantity is directly proportional with the saliva pH descent because of the characteristic of the bacteria that can produce acid and grow up well in acid circumstance. The bacteria can produce acid (aciduric) and live in acid circumstance (acidogenic) so that they have the potency to form acid extensively. ...
Peatlands in Borneo is the second which the pH is 32% below normal that is 2-5, the pH of the acid contained in the peat water can trigger the acid environment of the oral cavity resulting in increased aerobic bacteria of the oral cavity. Most small communities of South Kalimantan who lives inland which is unreachable with clean water still use peat water for daily necessities. The purpose of this study was to determine the effect of peat water to the number of aerobic bacteria colonies of the oral cavity. This study used the quasi-experimental research design with pre-posttest control group design. The study sample consisted of 20 students of Faculty of Dentistry, Lambung Mangkurat University. The research used peat water after mouth rinsing with 10 ml of water and then the number of aerobic bacteria colonies which were present in bacterial growth media was counted. The result of this study showed that the result of paired t-test showed no significant differences between the groups before and after rinsing with peat water (p = 0.001) (p <0.005). Based on the research we conclude that the peat water may cause an increasing in the number of colonies of aerobic bacteria of the oral cavity.
... Bone cells play a fundamental regulatory role in coupling bone formation and resorption and in initiating/preventing mineralization. (37) Therefore, the absence of viable cells can lead to the uncontrolled (both in terms of quantity and structural organization) precipitation of Ca and P at the bone-bacteria interface, especially since many body fluids, such as blood and saliva, are supersaturated with respect to calcium phosphate precipitation. (38,39) That mineralization is thermodynamically and kinematically favored in the absence of specific inhibitors is observed in pathological mineralization contexts such as atherosclerosis, (40) kidney stones, (41) and dental calculus. ...
... (43) On the other hand, an increased mineral content has been associated with MRONJ. (4,37) Regarding the second mechanism, although direct degradation of bone by biofilm pathogens is not yet widely recognized, the presence of bacteria at the interface with bone and of mineral-like nanosized particulate matter within and around them ( Figure 4E) supports an active role of bacteria in degrading . The interface appears as an electron-dense band (dotted line) that fades into a loosely organized region (asterisk) toward the resin space (B, corresponding to area marked by rectangle in A). ...
Medication‐related osteonecrosis of the jaw (MRONJ) is a known side effect of bisphosphonates (BPs). While bacterial infection is usually present, the etiology of MRONJ remains unknown. Herein, we apply a multimodal and multiscale (micro‐to‐nano) characterization approach to investigate the interface between necrotic bone and bacteria in MRONJ. A non‐necrotic bone sample was used as a control. Both necrotic and non‐necrotic bone samples were collected from the jaw of a female individual affected by MRONJ after using BPs for 23 years. For the first time, resin cast etching was used to expose bacteria at the necrotic site. The bone‐bacteria interface was also resolved at the nanoscale by scanning transmission electron microscopy (STEM). Nano‐sized particulates, likely corresponding to degraded bone mineral, were often noted in close proximity to or enclosed by the bacteria. STEM also revealed that the bone‐bacteria interface is composed of a hypermineralized front fading into a highly disordered region, with decreasing content of calcium and phosphorus, as assessed by electron energy loss spectroscopy (EELS). This, combined with the variation in calcium, phosphorus and carbon across the necrotic bone‐bacteria interface evaluated by scanning electron microscopy (SEM)‐energy dispersive X‐ray spectroscopy (EDX) and the lower mineral‐to‐matrix ratio measured by micro‐Raman spectroscopy in necrotic bone, indicates the absence of a mineralization front in MRONJ. It appears that the bone‐bacteria interface originates not only from uncontrolled mineralization, but also from the direct action of bacteria degrading the bone matrix.
... The use of FTIR spectroscopy in bone studies is widely documented [47][48][49][50][51][52]. Furthermore, any residual bone fragments may have been digested. ...
Paleontologists and archeologists reconstruct ancient ecosystems using data from carnivores’ food remains. Carnivores have evolved to employ two primary feeding strategies: consuming mostly meat and focusing on both meat and bones, and these strategies result in the production of different feces. Hyenas are exemplary meat-eaters and bone-crushers. While fecal characteristics like shape, color, size, and inclusions are often used for species identification, the detailed composition of hyena feces remains largely unexplored. To address this, we conducted a multimodal analysis of feces-like coprolites from four modern Hyaenid species, using scanning electron microscopy (SEM) and Fourier transform infrared spectrometry (FTIR). This approach allowed for the detection and quantification of the proportions of calcium phosphate/carbonate, silts, organic matter, and crystallinity in the coprolites. Our preliminary findings suggest that multivariate statistical analysis of these components could provide a reliable method for species identification based solely on fecal content, results which can be applied in research on fossil materials.
... Hydroxyapatite is the main inorganic content of bone. Bone is a biocomposite of inorganic component (50%-70%), organic component (20%-40%), water (5%-10%) and lipids (approximately 3%)(Rho et al., 1998;Boskey, 2007;Talal et al., 2020). ...
La fluorose osseuse est une pathologie liée à l’ingestion prolongée de grandes quantités de fluorure, qui entraine notamment une augmentation de la densité des os. Cette maladie sévit souvent à l’état endémique dans certaines zones volcaniques où les eaux souterraines contiennent des doses élevées de fluor. Cette étude vise à proposer une approche multidisciplinaire combinant observations paléopathologiques et analyses archéométriques pour le diagnostic de la fluorose osseuse des restes humains provenant de sépultures secondaires à crémation de la période romaine (IIe siècle av. J.-C. – Ier siècle apr. J.-C.). L’échantillon étudié est composé de 45 individus originaires de la ville de Cumes (Campanie, sud de l’Italie), dans la région volcanique des Champs Phlégréens. Les lésions pathologiques ont été enregistrées selon un protocole d’observations macroscopiques. La détection et les mesures de fluor ont été effectuées par Spectroscopie d’émission atomique de plasma induit par laser (LIBS). Les résultats ont permis de confirmer que les os des habitants de Cumes présentaient des concentrations élevées de fluor et des lésions pathologiques très probablement liés à la fluorose osseuse. 49 % des sujets étudiés a été classé dans les catégories de suspicion modérée à forte de fluorose, indiquant une potentielle intoxication environnementale. Cela est probablement liée au caractère volcanique de la région et à la consommation des eaux souterraines.
... However, low Zn feeding tended to reduce P and increase Ca in femur ash, raising the Ca-P molar ratio. The reduced P content in bone suggests a potential impact of Zn on the organic bone matrix, which contains various phosphorylated proteins (Boskey, 2007). These effects were however less strong than the effects of low P feeding on femur minerals themselves. ...
This study examined the effects of short-term dietary zinc (Zn) and phosphorus (P) variations on the mobilizable bone Zn pool and overall Zn status in adult laying hens. Forty-eight hens (50% Lohmann Brown Classic, 50% Lohmann LSL Classic) were housed in pairs (one hen per breed per pen) across 24 pens. The pens were randomly assigned to one of two dietary P levels (0.37% or 0.84% in DM) using a high-protein corn-soybean diet (11.4 MJ AME/kg, 21.5% CP) during a 14-day acclimatization period. Following acclimatization, pens from both P groups were further randomized into four dietary treatments in a 2 x 2 factorial design, varying in P levels (low vs. high) and Zn supplementation (28 vs. 131 mg/kg) over an 8-day experimental feeding phase. Performance metrics, egg production and quality, and tissue mineral concentrations (plasma, liver, bone, and eggs) were measured. Statistical analyses were performed using linear mixed models in SAS 9.4, incorporating random effects of pen nested within treatment group and fixed effects of dietary P, dietary Zn, breed, and their interactions. Tukey-corrected 95% confidence intervals were used to estimate effect differences, with significance set at P < 0.05. Performance metrics, including egg production and body weight, were unaffected by dietary treatments (P > 0.1), indicating no clinical symptoms of Zn deficiency. However, hens on low-Zn diets exhibited significant reductions in plasma Zn concentration (-0.83 mg/L; P = 0.0008) and liver Zn concentration (-6.78 mg/kg DM; P = 0.01), confirming subclinical Zn deficiency. Low-Zn diets also increased the femoral molar Ca:P ratio by 0.15 (P = 0.01), irrespective of dietary P supply. Interestingly, low-P diets led to a significant reduction in femur Zn content (-0.46 mg; P = 0.0009), regardless of Zn supplementation, following 21 days of reduced P feeding. These findings highlight the higher susceptibility of laying hens to phytate antagonism compared to broilers, as evidenced by measurable subclinical Zn deficiency under short-term Zn deprivation. Additionally, a temporary suspension of mineral P supply appeared to impair the mobilizable bone Zn pool. The underlying functional mechanisms driving these interactions remain unclear and warrant further investigation.
... In response to these challenges, there has been a surge of interest in bone substitute materials, 4 which include both inorganic and organic components that enhance structural integrity, stiffness, and mineral homeostasis. 5,6 Natural and synthetic polymers have become focal points in research on bone repair and regeneration due to their biocompatibility, mechanical strength, and biodegradability. 7 Natural polymers, such as collagen, chitosan, and hyaluronic acid, provide excellent biocompatibility and osteoconductivity, facilitating bone cell attachment and minimal immunogenic responses. ...
This study investigates novel biomaterials developed for bone regeneration, using cellulose and collagen type I matrices enhanced with hydroxyapatite or InterOss. These materials demonstrate significantly improved mechanical properties, notably the compressive modulus, indicating their potential for effective structural support in bone regeneration. Incorporating hydroxyapatite into these matrices markedly improves their physical properties, increasing the Brunauer–Emmett–Teller area and monolayer capacity, thereby facilitating superior cell adhesion and proliferation. This enhancement promotes more effective osteoblast activity and viability over extended periods compared to matrices containing InterOss. Furthermore, the scaffolds comprising cellulose modified with (3-amino-4-methylphenyl) boronic acid exhibit significantly enhanced antibacterial properties, effectively inhibiting both Gram-positive and Gram-negative bacteria, which is crucial for preventing post-surgical infections. Materials that incorporate hydroxyapatite (HA) have displayed a rougher and more intricate surface compared to those that include InterOss® particles, suggesting that HA promotes the development of an enhanced mineralized skeleton within the composites. Cytocompatibility studies revealed that the scaffold containing cellulose, collagen, and hydroxyapatite provided the most favorable environment for sustaining cell viability, with significant improvements noted from day 7 onwards. Despite initial cytotoxicity challenges, long-term exposure showed improved cell viability, suggesting degradation of cytotoxic products over time. This research underscores the clinical potential of these biomaterials in bone regeneration, highlighting their ability to enhance structural integrity, support osteogenic activity, and prevent bacterial infections, thus promising to improve patient outcomes in bone-related therapies.
... There are also separate processes of bone remodeling, regeneration, and growth that take place throughout a person's life. Osteogenesis is primarily characterized by calcification of the extracellular matrix (ECM), which normally occurs in human bones, teeth, and cartilage and serves to strengthen these tissues [8]. However, calcification can also occur in other tissues-aging ...
The transcription factor Runx2 plays a crucial role in regulating osteogenic differentiation and skeletal development. This factor not only controls the expression of genes involved in bone formation, but also interacts with signaling pathways such as the Notch pathway, which are essential for body development. However, studies have produced conflicting results regarding the relationship between Runx2 and the Notch pathway. Some studies suggest a synergistic interaction between these molecules, while others suggest an inhibitory one, for example, the interplay between Notch signaling, Runx2, and vitamin D3 in osteogenic differentiation and bone remodeling. The findings suggest a complex relationship between Notch signaling and osteogenic differentiation, with ongoing research needed to clarify the mechanisms involved and resolve existing contradictions regarding role of Notch in this process. Additionally, there is increasing evidence of contradictory roles for Runx2 in various tissues and organs, both under normal conditions and in pathological states. This diversity of roles makes Runx2 a potential therapeutic target, offering new directions for research. In this review, we have discussed the mechanisms of osteogenic differentiation and the important role of Runx2 in this process. We have also examined its relationship with different signaling pathways. However, there are still many uncertainties and inconsistencies in our current understanding of these interactions. Additionally, given that Runx2 is also involved in numerous other events in various tissues, we have tried to comprehensively examine its functions outside the skeletal system.
... The basic mineral composition of bones is calcium phosphate, often from biological apatite phosphate. Then, there are many variances between biological apatite and geological apatite: formation conditions, the biological apatite has a small crystal size, a high substitution of phosphate (PO 4 −3 ) by carbonate (CO 3 −2 ), and a substantial deficiency of hydroxide ions (OH); all these characteristics lead to enhancement of the solubility of biological apatite (Boskey 2007;Wopenka and Pasteris 2005). Bone char is a product that mostly contains hydroxyapatite [Ca 10 (PO 4 ) 6 (OH) 2 ] 70-76%, carbon 9-11%, and calcium carbonate 7-9% as well as the existence of acid soluble ash < 3%, Calcium sulfate 0.1-0.2%, and iron as Fe 2 O 3 < 0.3%. ...
Recycling slaughterhouse waste such as bone and converting it into bone char is a promising environmentally friendly, low-cost strategy in a circular economy and an important source of phosphorus. Therefore, this review focused on the impacts of bone char on the availability, dynamics, and transformations of phosphorus in soils as well as plant growth and utilizing bone char in remediating contaminated soils by heavy metals. Bone char is material produced through bone pyrolysis under limited oxygen at 300-1050 °C. Bone char applications to the soils significantly increased phosphorus availability and plant growth. Agricultural practices such as co-applying organic acids or sulfur or nitrogen fertilizers with bone char in some soils played an important role in enhanced phosphorus availability. Also, co-applying bone char with phosphate-solubilizing microorganisms enhanced plant growth and phosphorus availability in the soils. Applying bone char to the soils changed the dynamics and redistribution of phosphorous fractions, enhanced fertility, promoted crop growth and productivity, reduced heavy metals uptake by plants in contaminated soil, and decreased heavy metals bioavailability. Bone char has shown positive performance in remediating soils contaminated by heavy metals. Bone char proved its efficiency in sustainable agriculture and practical applications as an alternative source of phosphate fertilizers, it is safe, cheap and helps in remediating contaminated soils by heavy metals. Using bone char as a slow-release fertilizer is potentially beneficial because it reduces the hazard of excessive fertilizing and nutrient leaching which have negative impacts on the ecosystem.
... Bones' organic component is made of collagen plus noncollagenous proteins. The inorganic component contains a mineral analog of hydroxyapatite, including various substitutions and vacancies found in the crystal matrix [1]. Bone DNA preservation is linked to organic and inorganic bone components [2][3][4][5], and the DNA molecule creates complexes with both hydroxyapatite [6] and collagen [7]. ...
... Generally, bones consist of a strong and dense cortical part and a porous, flexible trabecular part. Cortical bone prevails in long bones, while rest of bones are formed by trabecular bone, covered by relatively thin compact bone [23][24][25][26]. ...
Molecular characteristics of skeletal remains were studied utilizing ATR-FTIR spectroscopy, focusing on comparisons between mature adult and immature non-adult skeletal elements. To cover the intra-skeletal variability, different types of bones were analysed. The objective was to identify significant differences between various skeletal elements of adults and non-adults. Additionally, the correlation between observed differences and DNA preservation was investigated. Despite exposure to taphonomic factors, findings indicate minimal diagenetic changes or a well-balanced alteration in mineral and collagen within bones. The identified differences primarily reflect functional and structural differences among various skeletal elements. Significant differences between adults and non-adults, or lack of it, is attributed to different paths of bone maturation from childhood to adulthood. High DNA preservation in non-adult petrous bones was attributed to the interplay between DNA and carbonates, both occupying hydroxyl sites in the lattice. Conversely, lower DNA content in other bones, especially non-adult bones, was correlated with high relative concentrations of collagen, in which DNA is less stable and more prone to degradation. This study highlights the importance of skeletal variation (inter, intra, developmental stage) when assessing the preservation state of the remains and choosing samples for further analyses such as DNA. For the first time, differences between mature adult and immature non-adult bones are included.
... [13] Indeed, tooth-derived dentin shares similarities to alveolar bone in terms of physicochemical properties, such as calcium and phosphate concentrations as well as overall inorganic and organic composition. [14] These characteristics have driven the production of autogenous particulate dentin (APD) and gradually developed into a set of standard preparation protocols. ...
Background
Autogenous particulate dentin (APD) has been used as a bone graft material for bone augmentation, but the specifics of its effect on alveolar ridge preservation (ARP) are uncertain. The aim of this study was to investigate the clinical and histomorphometric performance of APD compared with blood clot healing or other grafted materials in ARP.
Methods
MEDLINE, Embase, Web of Science, Scopus and the Cochrane Library and citation databases were searched until August 2, 2023 to identify randomized controlled trials that employed APD for ARP. Two independent meta-analyses were performed based on the different control groups (Group I: blood clot healing; Group II: other grafted materials). Weighted or mean differences (MDs) and corresponding 95% confidence intervals (CIs) were calculated. The protocol was prospectively registered with PROSPERO (CRD42023409339).
Results
A total of 238 records were identified, of which ten studies with 182 participants were included. The meta-analysis indicated that APD resulted in fewer changes in horizontal ridge width (Group I: MD = 1.61, 95% CI 0.76–2.46; Group II: MD = 1.28, 95% CI 1.08–1.48) and labial bone height (Group I: MD = 1.75, 95% CI 0.56–2.94; Group II: P < .05) than the control treatments. Regarding histomorphometry, APD yielded a satisfactory proportion of vital bone area (MD = 10.51, 95% CI 4.70–16.32) and residual material area (MD = −8.76, 95% CI −12.81 to −4.71) in Group II, while there was no significant difference in Group I. Moreover, none of the secondary outcomes were significantly differed between groups.
Conclusion
Within this study limitations, APD effectively maintained the horizontal and vertical dimensions of the extraction sockets and exhibited favorable osteogenic properties and degradation capacity. Further well-designed randomized controlled trials with larger samples and longer follow-up periods are needed to evaluate whether APD is superior to other substitutes for ARP.
... Bioapatites, consisting of broken fragments and teeth of marine creatures, have grain lengths ranging from 50 μm to 500 μm (Kon et 2021; Sa et al., 2018;Liao et al., 2022). The broken fragments and teeth are mainly composed of nanosized hydroxyapatite crystals interwoven with matrix proteins such as collagen (Elliott, 2002;Boskey, 2007;Liao et al., 2019aLiao et al., , 2022Yasukawa et al., 2022). The ΣREY of the studied bioapatites decreased significantly from the root to the tip (varying from 10 4 μg/g to 10 2 μg/g) within the well-preserved teeth (Fig. 8), which reveals the spatial heterogeneity of REYs distribution in the fossil grains. ...
... Various age estimation methods are utilized to assess the level of physical growth and development in these individuals (29). Teeth contain building blocks such as calcium, phosphate, and magnesium, which are similar to bone structure and can also be utilized in these methods (30,31). ...
Purpose:
The present study aims to assess the effect of sports on the dental maturity using two different dental age assessment methods and to determine whether there is a significant correlation between dental maturity and body mass index.
Materials and methods:
One hundred and thirty-eight students from Sports High School (study group) and 126 from Fine Arts High School (control group) with standard panoramic radiographs were included in the study. Dental age was assessed using Nolla's and Haavikko's methods. Demographic information regarding the weekly training hours and sports age of the study group participants was gathered. Body mass index values of all participants were calculated. Factorial analysis of variance and Tukey's test were performed and the Pearson correlation coefficient was calculated.
Results:
The mean age of the students was 15.93 ± 1.13 years for the study group and 15.99 ± 1.09 years for the control group. Mean dental age values were lower than the mean chronological age values in both high schools. The difference between the dental and chronological ages was insignificant in Sports High School (p > 0.05). Differences in the body mass index between high schools and genders were statistically significant (p<0.05). Significant correlations were detected between the sports and dental ages and between dental age and body mass index values.
Conclusion:
Sports participation could have positive effects on the dental maturity as well as on the bone development.
... Bones and teeth consist of a heterogeneous composite material containing, in decreasing order, a mineral phase (carbonate hydroxyapatite, Ca 10 (PO 4 ) 6 (OH) 2 ), an organic phase (~90 % type I collagen, ~5% non-collagenous proteins (NCPs), ~2% lipids by weight) and water (Young, 2003;Boskey, 2007). In general, isotopic studies of bone and tooth tissues can be realized on either collagen or bioapatite. ...
... In general, dentin presents many similarities to bone tissue, thus justifying the possibility of using it as bone substitute material. 12 Moreover, the higher density of tooth materials, as compared to the bone, could allow to achieve a slow resorption rate which is favorable in the bone healing process. 13 Several techniques and devices were proposed and described for using the tooth material as bone substitute. ...
Introduction: Both bone and dentin consist of 35% of proteins (90% collagen type I and 10% proteins incommon with bone) and of 65-70% inorganic portion (hydroxyapatite crystals). International literaturedemonstrated, over the years, that tooth material could be a valid alternative to xenograft. To this aim manysurgical techniques and mechanical devices were introduced to use the autologous tooth as bone substitute.
Method: The present study aim was to show a new grafting material obtained by an innovative device andinvolved 525 patients. All the patients showed one or more hopeless teeth. After atraumatic tooth extraction,the baseline socket buccal-lingual and vertical morphology dimensions were recorded. The whole tooth of thepatient was carefully cleaned, and any filling materials were removed. The tooth was cut in small pieces, driedand it was inserted in the device (Tooth Transformer, Milan, Italy). In 25 minutes, this totally automated device,returns a natural demineralized particle graft material. The obtained material was grafted in the bone defectand covered by collagen membrane. After 4 months of healing 507 dental implants were inserted.
Results: Twelve months after loading, only 10 dental implants failed (2.3%), with a 98% overall implant survivalrate. The peri-implant bone loss was 0.42 ± 0.79 mm at mesial sites and 0.22 ± 0.37 mm at distal ones. Noinfective complications were observed, and all defects were filled by new bone formation. The bonearchitecture was maintained, and surgeons found no tactile differences when drilling these sites in respect withthe native bone. The vital bone percentage (VB%) was 37.9 ± 21.9 % in maxillary sites and 38 ± 22% inmandibular ones. The residual graft particles were extremely low with a mean percentage of 7.5 ± 11.9. Thehistological analysis revealed a close contact between demineralized tooth particle and surrounding bone.
Conclusion: The present study demonstrated that autologous tooth graft could be use with success in freshpost extractive socket regeneration. Results showed a predictable bone maintenance without any infective orinflammatory reaction. The histologic analysis revealed new bone formation and remodeling phenomena of thetooth particles. The extracted tooth of the patient represents an incredible source of natural material for bonegrafting procedures.
... The bone contains calcium phosphate classified as biogenic crystalline apatite which can be differentiated from geological apatite-exists in rock phosphates-by its small crystal size, high carbonate substitution, substantial OH deficiency, vacancies in the lattice, and the resultant increased solubility. All these factors cause high solubility of the biological apatite (Boskey 2007;Wopenka and Pasteris 2005). Several studies observed that the amount of available phosphorus in soils with bone char application was higher than the phosphate rock (Warren et al. 2009;Vassilev et al. 2013). ...
Several chemical properties of alkaline soils play an important role in dissolving phosphate minerals, which greatly affect the phosphorous availability to plants. The current study was carried out to assess bone char application on the availability and distribution of phosphorus in some alkaline sandy soils. This incubation experiment was performed by selecting some alkaline soils from different locations in Upper Egypt: Arab El-Awamer (Assiut Governorate), West El-Minia (El-Minia governorate), and New Valley Governorate. Bone char was applied at a dose of 4 g kg−1 soil. The incubation periods lasted for 7, 16, 35, 65, and 84 days. Phosphorus availability in Arab El-Awamer soil increased significantly with applying bone char and was greatly influenced by soil chemical properties and incubation periods. Bone char addition caused a relative increase of available phosphorous in the sequence as follows: Arab El-Awamer soil ˃ New Valley soil ˃ West El-Minia soil. Available phosphorous showed a negative correlation with electrical conductivity, soluble calcium, and soluble sulfate. A significant increase of NH4Cl-Pi, NaHCO3-Pi, NaOH-Pi, HCl-Pi, and residual P fractions occurred in some soils with bone char application. Phosphorus fractions distribution in all soils followed: HCl-P ˃ residual P ˃ NaHCO3-P ˃ NaOH-P ˃ NH4Cl-P. The correlation between phosphorus availability and phosphorus fractions was positive. Our results focus on the importance of using bone char as an amendment in P-poor alkaline soils for improving phosphorus availability. So, bone char is an effective technique for sustainable agriculture because it is a clean and renewable resource of phosphate fertilizers.
... L'os est formé à partir (1) d'une matrice organique (25%) appelée ostéoïde, composée essentiellement de collagène de type I (90%), mais aussi d'autres protéines comme l'ostéonectine ou l'ostéocalcine, une protéine synthétisée par les ostéoblastes qui sont les cellules responsables de la mise en place et du renouvellement de l'os ; (2) d'une matrice minérale (70%) très riche en phosphate de calcium sous forme d'hydroxyapatite de calcium Ca 10 (PO 4 ) 6 (OH) 2 ) et (3) à partir de cellules osseuses spécifiques (5%) (Ostéoblastes et ostéoclastes) et de l'eau. Le processus d'ossification des os longs chez l'humain débute au cours du 3è mois de la vie embryonnaire et s'achève pratiquement vers l'âge de 25 ans (Beniash, 2011;Boskey, 2007;Boskey & Mendelsohn, 2005), cité dans (Balasse et al., 2015). ...
Les genres Bos et Bison constituent la sous-tribu des Bovina et incluent plusieurs lignées de bovins. Les espèces domestiques et sauvages appartenant à ces deux genres auraient divergé au Pléistocène inférieur. L’histoire génomique évolutive récente de Bos et Bison ne reflète qu’imparfaitement les liens phylogénétiques anciens car ceux-ci sont éclipsés par les événements récents, en particulier la quasi-extermination aux 19ème et 20ème siècles des bisons américains (Bison bison) et bisons européens (Bison bonasus), respectivement, ainsi que la disparition au 17ème siècle de l’aurochs, ancêtre des bovins domestiques actuels. Dans le but de clarifier l’histoire évolutive de ces deux genres, nous avons mis en place une approche paléogénomique permettant de séquencer l’ADN ancien extrait à partir de spécimens fossiles des genres Bos et Bison. L’objectif était de reconstruire les mitogénomes et les génomes nucléaires de restes fossiles datant du Pléistocène à l’Holocène, témoins des événements évolutifs précédant les événements les plus récents qui ont remodelé la diversité génétique des populations modernes. Nous avons ainsi analysé des restes fossiles du Néolithique jusqu’à l’ère moderne, témoins de l’impact de la domestication sur la structuration génétique des bovins. Nous avons adapté les méthodes d’analyse de l’ADN aux caractéristiques particulières de l’ADN ancien pour maximiser la récupération de l’ADN ancien à partir des restes fossiles et convertir efficacement les fragments d’ADN contenus dans l’extrait fossile en banques génomiques pour le séquençage de nouvelle génération (NGS). Nous avons aussi optimisé un protocole de capture du génome mitochondrial de bovins anciens pour augmenter son efficacité avec des échantillons mal conservés. L’optimisation méthodologique nous a permis d’obtenir la séquence de 20 mitogénomes complets de bisons européens et bisons des steppes datant du Pléistocène moyen jusqu’aux aux temps modernes et 98 mitogénomes complets d’aurochs et de bovins domestiques eurasiatiques et africains datant du Pléistocène supérieur jusqu’au Moyen Âge. Nous avons reconstruit l’histoire évolutive de Bos et Bison à travers une analyse phylogénétique qui rassemble 279 mitogénomes anciens et 671 mitogénomes modernes des Bovina. Ceci nous a permis d’établir une datation robuste des radiations phylogénétiques et de reconstruire les dynamiques des populations bovines pendant les 50 000 dernières années.Nous avons identifié un nouvel haplogroupe mitochondrial d’aurochs rassemblant des échantillons du Pléistocène supérieur originaire de l’Europe de l’Ouest. Cet haplogroupe s’est séparé le premier des lignées d’aurochs européens et proche-orientaux, des bovins domestiques eurasiatiques et africains ainsi que des zébus. Ceci met en évidence une dynamique complexe des populations bovines ancestrales au Pléistocène moyen et supérieur ainsi que les liens partagés entre les populations eurasiatiques et du sous-continent indien. L’analyse d’échantillons précédant et suivant le dernier maximum glaciaire, entre 30 000 et 12 000 ans, et les modélisations démographiques utilisant les mitogénomes anciens et actuels des différentes lignées ont permis d’évaluer l’impact de cette glaciation sur la dynamique des tailles effectives des populations d’aurochs. Notre étude permet de réévaluer les causes du goulot d’étranglement précédemment attribué à la domestication des aurochs. Nous avons aussi caractérisé en parallèle les génomes d’une vingtaine de bisons qui permettront de comparer l’évolution de ces deux lignées cousines, l’une ayant été domestiquée et l’autre non. L’ensemble du travail réalisé permet d’établir une base solide pour étudier les changements génomiques associés à la domestication des bovins.
... The inorganic part is represented by the mineral analogue of hydroxyapatite, with a variety of substitutions and vacancies in the crystal matrix, numerous in the bone and dentin mineral and less numerous in the enamel apatite. 36 On the nanoscale, crystals of bone and dentin are similar in size (20-50 Â 12-20 nm), whereas enamel has 10 times larger crystals. 37,38 Bones in the human skeleton form five main categories: long, short, flat, irregular and sesamoid bones, which differ based on their shape and function (Table 1). ...
Spectroscopy of skeletal tissues is increasingly used in various fields, including legal medicine, forensic science, and archaeology. As it is fast and technically and financially affordable yet accurate and widely applicable, spectroscopy is often used when investigating skeletal tissues. Despite its usefulness, the heterogeneity of skeletal tissues highly affects their chemical composition and complicates the interpretation of the spectroscopy results. Though the research on the use of spectroscopy and skeletal tissues from various contexts is growing, little is known regarding the differences in the chemometric indices caused by intra‐skeleton variability. The objectives were a comparison of the chemometric indices between teeth and bones, between different bone classes, and between the skeletal elements within a bone class as well as an attempt to correlate the observed similarities or differences in chemometric indices to the functional or structural differences of skeletal elements. Different skeletal elements of three individuals were analysed with attenuated total reflectance (ATR)–Fourier Transform Infrared (FTIR) spectroscopy and compared. Significant differences between the chemometric indices of the bones and teeth were observed and meaningfully correlated with their structural differences. Though more subtle and harder to understand, significant differences were also observed between and within the bone classes and were tentatively correlated with their structural and functional differences. The observed variability agrees with other studies that stress the importance of intra‐skeleton variability, which should be acknowledged when using spectroscopy to investigate skeletal tissues.
... Implantable biomaterials are often designed as porous scaffolds that serve as threedimensional (3D) templates to support and guide the healing of osseous tissue at the injured site [1]. Hydroxyapatite is one of the most popular biomaterials for bone substitution due to its similarity with the calcium-phosphate mineral phase of natural bone [2]. Hydroxyapatite has been clinically used for decades in multiple forms, including micro-sized and nanosized particles, coatings on metallic endoprostheses, composites, injectable pastes for spine surgery and porous scaffolds [3]. ...
Porosity is a key feature in dictating the overall performance of biomedical scaffolds, with special relevance to mechanical properties. Usually, compressive strength and elastic modulus are the main parameters used to determine the potential mechanical suitability of porous scaffolds for bone repair. However, their assessment may not be so easy from an experimental viewpoint and, especially if the porosity is high, so reliable for brittle bioceramic foams. Hence, assessing the relationship between porosity and mechanical properties based only on the constitutive parameters of the solid material is a challenging and important task to predict the scaffold performance for optimization during design. In this work, a set of equations was used to predict the compressive strength and elastic modulus of bone-like hydroxyapatite scaffolds produced by digital light processing-based vat photopolymerization (total porosity about 80 vol.%). The compressive strength was found to depend on total porosity, following a power-law approximation. The relationship between porosity and elastic modulus was well fitted by second-order power law, with relative density and computational models obtained by numerical simulations.
... Bone mineral is AB-type, containing both types of substitutions, with the degree of A-type substitution observed to depend on the age and species of the bone tissue [40]. Increased CO 3 2− content in bone apatite has been linked to reduction in crystallinity and to the platelike habit and nanometer-scale of primary crystallites, which impart high biological activity, including ease of resorption in vivo [30,35,[41][42][43]. Importantly for the current work, A-type substitutions have been observed to reduce the crystallinity of apatite more than B-type [39]. ...
Biochars are a class of carbonaceous materials possessing high degrees of structural and chemical disorder in both organic and inorganic constituent phases. Despite this disorder, and in some cases because of this disorder, biochars have shown strong performance in adsorbing and even sequestering contaminants from soil, surface water and air. Biochar is the carbonaceous, solid product of heating carbonaceous feedstock in an oxygen-limited environment above 250°C, usually sourced from inexpensive, locally available agricultural and forestry wastes which can otherwise be difficult and expensive to dispose of. Biochar possesses attractive functional properties like high specific surface area, high micropore volume, and tunable surface chemistry which are key to performance in separation technologies and environmental remediation. In this work, two high-performing biochars were investigated: one from cottonwood feedstock and one sourced from locally available bovine bone waste. In the wood-based biochar, the synergistic impacts of potassium content and lignin microstructure were investigated for their role in determining biochar structure and function. The performance of these biochars was tested in dynamic adsorption of gaseous ammonia, a growing threat to human and environmental health, in which all biochars outperformed a commercial activated carbon. Breakthrough times showed no correlation with surface area of the adsorbents, contrary to expectation. Biochar sourced from pyrolyzed bovine bone has shown strong performance against a range of other materials in removing Cu2+ from acid mine waste. In-depth characterization of the mineral and organic phases of this novel biochar revealed that disorder may be key to its strong performance in Cu2+ removal.
... Bone mineral is AB-type, containing both types of substitutions, with the degree of A-type substitution observed to depend on the age and species of the bone tissue [40]. Increased CO 3 2− content in bone apatite has been linked to reduction in crystallinity and to the platelike habit and nanometer-scale of primary crystallites, which impart high biological activity, including ease of resorption in vivo [30,35,[41][42][43]. Importantly for the current work, A-type substitutions have been observed to reduce the crystallinity of apatite more than B-type [39]. ...
Bone waste is a problematic slaughterhouse waste typically disposed of in landfills. The pyrolyzed product of this waste shows strong potential in mine and industrial waste water remediation and work is needed to identify chemical and structural parameters which drive performance. Diffuse Reflectance Fourier Transform Spectroscopy (DRIFTS) was used to probe carbonate (CO 3 ²⁻ ), phosphate (PO 4 ³⁻ ) and hydroxyl (OH ⁻ ) environments of mineral phases and functional group chemistry in carbonaceous phase, revealing a potentially synergistic functionality between the two in bone char. CO 3 ²⁻ and water substitutions in the mineral lattice were found to persist after pyrolysis to 750 °C, and more soluble non-apatite calcium phosphate phases were observed using second derivative analysis of the v 3 PO 4 ³⁻ band. Nitrogen-rich functional groups were found in the carbonaceous phase which are associated with complexation of aqueous metals, and ordered aromatic clusters identified by Raman spectroscopy indicate a porous carbon skeletal structure to promote metals adsorption and complexation. These results point to unique chemical and structural features of bone char which are not easily replicated by synthetic carbonated apatite or activated carbon and which contribute to the excellent aqueous metals removal power of bone char.
Graphical Abstract
... Bone is a complex and heterogeneous composite mainly composed of an inorganic phase (mineral), organic phase (collagen, non-collagenous proteins) and water. [1]. Understanding the spatial structure and chemical composition of bone at different scales is of great significance for elucidating its biomineralization mechanism, mechanical support, bone pathological treatment and bone scaffold development. ...
... In general, dentin presents many similarities to bone tissue, thus justifying the possibility of using it as bone substitute material. 12 Moreover, the higher density of tooth materials, as compared to the bone, could allow to achieve a slow resorption rate which is favorable in the bone healing process. 13 Several techniques and devices were proposed and described for using the tooth material as bone substitute. ...
Background:
An effective regenerative protocol is key to reestablish and maintain the hard and soft tissue dimensions over time. The choice of the graft material and its properties also could have an impact on the results. To prevent alveolar ridge dimensional changes, since numerous graft materials have been suggested and in the past years, a growing interest in teeth material has been observed as a valuable alternative to synthetic biomaterials.
Aim:
The aim of the study was to explore the histomorphometric outcomes of tooth derivative materials as used as bone substitute material in socket preservation procedure.
Methods:
After alveolar socket preservation (ASP) procedures using autologous demineralized tooth as graft material prepared by means of an innovative device, was evaluated. A total of 101 histological samples, from 96 subjects, were analyzed by evaluating the total amount of bone (BV), residual tooth material (residual graft, TT), and vital bone (VB). The section from each sample was then split in nine subsections, resulting in 909 subsections, to allow statistical comparison between the different areas.
Results:
It was not noticed a statistically significant difference between maxillary and mandibular sites, being the amount of VB in upper jaw sites 37.9 ± 21.9% and 38.0 ± 22.0% in lower jaw sites and the amount of TT was 7.7 ± 12.2% in maxilla and 7.0 ± 11.1% in mandibles. None of the other considered parameters, including defect type and section position, were statistically correlated to the results of the histomorphometric analysis.
Conclusions:
ASP procedure using demineralized autologous tooth-derived biomaterial may be a predictable procedure to produce new vital bone potentially capable to support dental implant rehabilitation.
... Pulp-dentin complex is present in the inner layer consisting of dentin as the immediate layer after enamel and pulp having all the capillaries supplying blood and nerve to the teeth. Cementum covers the root surface to maintain dental and periodontal attachment (Boskey, 2007). For dentin and cementum, almost 90% of these structures are made up from collagen, specifically from collagen type I. On the other hand, nearly 90% of the enamel structure is composed of non-collagenous protein (Margolis et al., 2014). ...
Oral disease has been a worldwide concern as the incidence and cost of treatment continues to rise. Management of the disease is challenging as success is often influenced by an individual’s lifestyle and diet. Nigella sativa (N. sativa) or black seed is a medicinal plant that has received growing interest due to its effectiveness against various conditions including cardiovascular disease, diabetes, cancer, as well as infectious diseases caused by bacterial, viral, and fungal infections. This narrative review studies N. sativa that has also shown great potential in dental health attributed to its role in stimulating the process of remineralization. Apart from that, N. sativa promotes healing of oral tissues as it induces the differentiation potential of heterogeneous cell populations in periodontal ligament cells. The anti-osteoporotic, antioxidant and anti-inflammatory properties of N. sativa also improve periodontal healing, particularly by preventing further destruction of bone components. This article discusses the occurrence of periodontitis and the therapeutic role of N. sativa with emphasis on the regulation of genes, for instance, the alkaline phosphatase (ALP) that is involved in tissue specialization and remineralization. It is speculated that the activity of N. sativa in remineralization can be enhanced by combination with other commonly used periodontitis antibiotics such as doxycycline. N. sativa is purported to induce periodontal tissue regeneration whilst minimizing toxicity. Thus, it may serve as an alternative or enhance the existing treatment for periodontitis when administered as a combined formulation.
The human brain can both synthesize minerals in situ and accumulate exogenous phases from the surrounding environment. Some of the biogenic phases may represent evolutionary remains, whereas others are crucial for many physiological functions of the neurological system. Yet an excess concentration of these minerals in the brain may be a precursor and/or a consequence of several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases. In this regard, there is very little in the literature that is focused on the minerals and mineraloids present in the human brain and on their physicochemical state. The gap in the literature is particularly wide for nanoscale and sub-nanoscale compounds. This review compiles the most significant research on minerals and mineraloids in the brain, the related neurodegenerative diseases, and their relationship with urban pollution. Here, we describe the strong link between neurodegenerative diseases and the presence of biogenic and exogenous minerals and mineraloids. Additionally, we highlight the importance of medical mineralogy for investigating diseases related to such phases. Future research must focus on not only the mineralogical characterization of particles in the brain but also the alteration and transformation of these particles in specific media and different locations in human brain cells and tissues. Further studies should attempt to perform nanoscale to atomic-scale characterization of the structure, the surface, the valence state, and the electrical and magnetic fields of the particles of interest.
Tough soft/hard composites were created, inspired by bony multiple sacrificial structures through ionic bonding, fracture of the ceramic skeleton, and interactions between the new surface of fracture skeleton and hydrogel.
Before employing a biomedical material in medical applications, a researcher must possess comprehensive knowledge regarding its chemical, physical, biological, structural, and mechanical properties. Hydroxyapatite (HAp, Ca 10 (PO 4 ) 6 (OH) 2 ) is a vital constituent of the calcium orthophosphate group. The material exhibits good dielectric and biological compatibility, diamagnetic behavior, thermal stability, osteoconductivity, and bioactivity. Additionally, it has a Ca:P molar ratio of 1.67. Because HAp has a chemical composition that is quite similar to normal bone and teeth, it has the potential to be used as a material for implant implantation in fractured portions of the human skeletal system. Many ways for generating HAp nanoparticles have been found as a result of the increasing usage of HAp in medicine. The conditions under which HAp is generated determine its physical and chemical properties, crystalline structure, and form. This study provides detailed information on the HAp’s characteristics and manufacturing procedures, as well as revealing the structure and its properties.
Surgery is required to restore bone loss brought on by regenerative periodontal diseases while retaining the patient's aesthetics. The bone deficits caused by periodontal disease have been repaired using a variety of transplant materials. One of the graft materials used is dentin since it resembles bone in terms of both organic and inorganic components. In order to evaluate the viability of dental grafts, this study intended to count the osteoblast cells that were still alive after a specific therapy. Osteoblast cell cultures in 42 well plates were employed in this work. The 42 well plate cell cultures were separated into seven groups for 24hour examinations and seven groups for 48 hour examinations in order to examine the cells using the MTT assay. Each group contained control cells, control media devoid of cells, and the treatment group, which received tooth transplant at doses of 8, 4, 2, 1, and 0.5mg/mL. Using an ELISA reader with a 595nm wavelength, the optical density of these cells was used to determine the viability of the cells. There are more than 50% of osteoblast cells in all concentrations, which is indicated by the number of these cells. The Shapiro-Wilk, Levene, and Oneway Anova tests were performed to assess the normality, uniformity, and degree of group differences in the data. This study demonstrates the biocompatibility of the tooth graft and the osteoblast cells.
Understanding how animals store and recycle nutrients is a major question in ecological stoichiometry, a field that applies mass‐balance to ecological and physiological processes. However, ecological stoichiometry has thus far failed to accurately predict elemental demand and release in vertebrates.
Because they invest in bone, a tissue mineralized with calcium phosphate, vertebrates are phosphorus (P) rich, allowing them to uniquely impact P cycling. Nonetheless, bone's impact goes further than merely changing vertebrate body elemental content.
We propose a potential guiding hypothesis for vertebrate P stoichiometry called the ‘Vertebrate Bone Hypothesis (VBH)’. The VBH has three components: (1)Bone strongly impacts vertebrate whole‐body %P and N:P. (2) Bone is a P storage tissue that acts in elemental homeostasis. (3)Bone does not have constant elemental content.
To characterize this hypothesis, we integrate bone physiology with stoichiometric principles, and we systematically review quantitative bone measurements to showcase cryptic diversity in vertebrate P content.
Finally, we apply the characteristics of the VBH to ontogeny and reproduction, both of which impact bone physiology and elemental demand, to demonstrate the context dependency of bone's stoichiometric impact.
Read the free Plain Language Summary for this article on the Journal blog.
The stable calcium (Ca) isotopes offer a minimally invasive method for assessing Ca balance in the body, providing a new avenue for research and clinical applications. In this study, we measured the Ca isotopic composition of soft tissues (brain, muscle, liver, and kidney), mineralized tissue (bone), and blood (plasma) from 10 mice (5 females and 5 males) with three different genetic backgrounds and same age (3 months old). The results reveal a distinctive Ca isotopic composition in different body compartments of mice, primally controlled by each compartment’s unique Ca metabolism and genetic background, independent of sex. The bones are enriched in the lighter Ca isotopes (δ44/40Cabone = − 0.10 ± 0.55 ‰) compared to blood and other soft tissues, reflecting the preferential incorporation of lighter Ca isotopes through bone formation, while heavier Ca isotopes remain preferentially in blood. The brain and muscle are enriched in lighter Ca isotopes (δ44/40Cabrain = − 0.10 ± 0.53 ‰; δ44/40Camuscle = 0.19 ± 0.41 ‰) relative to blood and other soft tissues, making the brain the isotopically lightest soft tissues of the mouse body. In contrast, the kidney is enriched in heavier isotopes (δ44/40Cakidney = 0.86 ± 0.31 ‰) reflecting filtration and reabsorption by the kidney. This study provides important insight into the Ca isotopic composition of various body compartments and fluids.
Despite significant efforts utilizing advanced technologies, the contentious debate surrounding the intricate mechanism underlying collagen fibril mineralization, particularly with regard to amorphous precursor infiltration and phase transformation, persists. This work proposes an amorphous calcium phosphate (ACP)‐mediated pathway for collagen fibril mineralization and utilizing stochastic optical reconstruction microscopy technology, and has experimentally confirmed for the first time that the ACP nanoparticles can infiltrate inside collagen fibrils. Subsequently, the ACP‐mediated phase transformation occurs within collagen fibrils to form HAP crystallites, and significantly enhances the mechanical properties of the mineralized collagen fibrils compared to those achieved by the calcium phosphate ion (CPI)‐mediated mineralization and resembles the natural counterpart. Furthermore, demineralized dentin can be effectively remineralized through ACP‐mediated mineralization, leading to complete restoration of its mechanical properties. This work provides a new paradigm of collagen mineralization via particle‐mediated phase transformation, deepens the understanding of the mechanism behind the mineralization of collagen fibrils, and offers a new strategy for hard tissue repair.
Shape, size, composition, and function of the bones in the human body vary on the macro, micro and nanoscale. This can influence changes caused by taphonomy and post-mortem preservation, including DNA. Highly mineralised compact bone is less susceptible to taphonomic factors than porous trabecular bone. Some studies imply that DNA can be better preserved in trabecular bone, due to remnants of the soft tissue or bacteria better digesting organic matter while not digesting DNA. The aim of this study was to understand the differences between compact (diaphyses) and trabecular (epiphyses) bone on a molecular level and thus the reasons for the better preservation of the DNA in the trabecular bone. The powder obtained from epiphyses and diaphyses of metacarpals and metatarsals was analysed using ATR-FTIR spectroscopy and compared. Samples with poorest DNA preservation originated from diaphyses, predominantly of metatarsals. They were characterised by higher concentrations of phosphates and crystallinity, while lower collagen quality in comparison to samples with the best DNA preservation. Epiphyses presented higher concentrations of better-preserved collagen while diaphyses had higher concentrations of carbonates and phosphates and higher crystallinity. Due to better-preserved collagen in the epiphyses, the soft tissue remnants hypothesis seems more likely than the bacteria hypothesis.
The bone-targeting mechanism of clinic bisphosphonate-type drugs, such as alendronate, risedronate, and ibandronate, relies on chelated calcium ions on the surface of the bone mineralized matrix for the treatment of osteoporosis. EGTA with aminocarboxyl chelating ligands can specifically chelate calcium ions. Inspired by the bone-targeting mechanism of bisphosphonates, we hypothesize that EGTA-derived carbon dots (EGTA-CDs) hold bone-targeting ability. For the target-oriented synthesis of EGTA-CDs and to endow CDs with bone targeting, we designed calcium ion chelating agents as precursors, including aminocarboxyl chelating agents (EGTA and EDTA) and bisphosphonate agents (ALN and HEDP) for the target-oriented synthesis of aminocarboxyl-derived CDs (EGTA-CDs and EDTA-CDs) and bisphosphonate-derived CDs (ALN-CDs and HEDP-CDs) with high synthetic yield. The synthetic yield of EGTA-CDs reached 87.6%. Aminocarboxyl-derived CDs and bisphosphonate-derived CDs retain the chelation ability of calcium ions and can specifically bind calcium ions. The chemical environment bone-targeting value coordination constant K and chelation sites of EGTA-CDs were 6.48 × 104 M-1 and 4.12, respectively. A novel method was established to demonstrate the bone-targeting capability of chelate-functionalized carbon dots using fluorescence quenching in a simulated bone trauma microenvironment. EGTA-CDs exhibit superior bone-targeting ability compared with other aminocarboxyl-derived CDs and bisphosphonate-derived CDs. EGTA-CDs display exceptional specificity toward calcium ions and better bone affinity than ALN-CDs, suggesting their potential as novel bone-targeting drugs. EGTA-CDs with strong calcium ion chelating ability have calcium ion affinity in simulated body fluid and bone-targeting ability in a simulated bone trauma microenvironment. These findings offer new avenues for the development of advanced bone-targeting strategies.
Biomolecular methods of taxonomic identification have been increasing in number more recently, but these are also affected to a greater or lesser extent by preservation depending on which biomolecule is being used, the most informative of these being with DNA. This chapter introduces what proteins are, how they are analyzed, and describes in general terms the types of information that can be obtained from proteomics, with a focus on archaeological bone. It presents an overview of the contributions that ‘palaeoproteomic’ techniques are making in archaeological investigations, and what they will likely continue to make in the near future. Although the use of Zooarchaeology by Mass Spectrometry has remained relatively limited during its infancy period, as descriptions of species peptide markers for several of the major taxonomic groups, particularly of fish, are still being published, several main research areas have benefitted from analytical developments.
As the quality of life improves, people pay more and more attention to health. They are concerned about the causes of diseases, and seek better treatments. The most common diseases are biomineralized diseases, four different kinds of typical examples among which are selected to elaborate their mechanisms and existing treatments. Whether it is tooth and bone in physiological mineralization or cartilage and blood vessel in pathological mineralization, they are all related to matrix vesicle (MV)-mediated biomineralization. MV-mediated biomineralization is the initial stage of biomineralization and the nucleation site mediating collagen mineralization. Definition, composition, biogenesis, and action mechanism of MVs are refined and expounded, especially a novel biomineralization pathway similar to exosome (EX) origin. Four differences are summarized to distinguish MVs and EXs. A series of treatments using MVs to solve biomineralized diseases such as tooth and bone defects, osteoarthritis and atherosclerosis are proposed, and the experimental extraction steps of MVs are summarized.
Many developed nations including the U.S.A. have increasingly older populations as birth rates have declined and life expectancy has increased over the twentieth century. A corresponding factor of two increase in demand for artificial joint and dental implants is anticipated over the next thirty years (Piehler 2000). The development of biomaterials for orthopaedic and dental implants with improved properties and durability in the human body is critical to deal with this aging population. Broadly speaking, the first-generation of biomaterials was bioinert, whereas bioactive and bioresorbable materials represented improved, second-generation materials. Still, one third to one half of the prostheses fail within 10–25 years and require a second surgery (Shirtliff and Hench 2003 and references therein). The challenge facing the development of improved orthopaedic and dental biomaterials for the future is to design materials that are biocompatible, capable of bearing high stress and loads, and that invoke positive cellular and genetic responses for the rapid repair, modification, regeneration and maintenance of the affected tissue in the human body, i.e., tissue engineering.
In this chapter, we will provide a brief history of the use of implants, and review the requirements that a biomaterial must fulfill to be used effectively as an orthopaedic or dental implant, the chemical composition-structure-activity of different types of silicate biomaterials including glasses and ceramics, the chemical reactions that occur at the silicate implant/solution interface involving inorganic ions and organic biomolecules (mainly proteins). We will also review studies that show the effects of different synthetic solutions, used experimentally to mimic human blood plasma, on in vitro tests of bioactivity. Our focus will be on dense silicate biomaterials that have up to ~20% porosity and high mechanical strength, in contrast to porous biomaterials with ~40–60% porosity and scaffold materials that have ~80% porosity and almost no mechanical strength. We will …
Previous freeze-etching studies of developing enamel revealed collinear arrays of spherical structures (approximately 50 nM dia) of similar width to the crystals of mature tissue. Concomitant with matrix degradation/processing, spherical structures became less distinct until, coincident with massive matrix loss, only crystal outlines were seen. More recently, using Atomic force microscopy technology, early crystals exhibited topology reminiscent of these collinear spherical structures. After matrix loss these were replaced by similarly sized bands of positive charge density on the crystal surfaces. The data suggest enamel crystals may form from mineral-matrix spherical subunits. Matrix processing may generate mineral nuclei and lead to their fusion and transformation into long apatite crystals. Support for this view derives from the appearance of short crystal segments in amelogenesis imperfecta (hypoplastic AI) or abnormally large crystals alongside 50 nM diameter spherical mineral subunits (hypomaturation AI). Mutation of matrix or processing enzymes leading to defective processing may have impaired mineral initiation, fusion, and subsequent growth.
This paper reviews our current state of knowledge of the roles the small leucine-rich proteoglycans (SLRPs) play in the formation of connective tissue and mineralised tissue matrices. Both, the SLRPs biglycan and decorin are highly expressed in extracellular bone matrix and there is now substantial evidence to support an increasing role for biglycan and decorin in influencing bone cell differentiation and proliferative activity. In addition decorin and biglycan have been implicated in regulating mineral deposition and crystal morphology, whilst decorin has also roles in organic matrix assembly. In order to further assess the role of these SLRPs during bone formation we have initiated studies investigating primary bone cell culture models from rats (bone marrow stromal cells, and bone cells from alveolar bone explants), and identified periods relating to cell proliferation, organic matrix deposition, remodeling of the osteoid, and mineral deposition. Analysis of mRNA levels and the nature of the proteoglycan demonstrated that dermatan sulphate substituted biglycan was expressed during phases relating to cell proliferation, ceased at early matrix deposition, and then biglycan was re-expressed at the onset of mineralisation, but was conjugated to chondroitin sulphate. Decorin was expressed later than biglycan, was associated with early matrix deposition, but then continued to the mineralisation stages. Again, dermatan sulphate-decorin prevailed earlier within osteoid matrix, whilst chondroitin sulphate-decorin predominated later within the mineralizing matrix. The nature of the GAG chain conjugated to SLRP and the timing of its expression would seem to dictate the functions biglycan and decorin play in bone formation.
The evolution of calcified tissues is a defining feature in vertebrate evolution. Investigating the evolution of proteins involved in tissue calcification should help elucidate how calcified tissues have evolved. The purpose of this study was to collect and compare sequences of matrix and bone gamma-carboxyglutamic acid proteins (MGP and BGP, respectively) to identify common features and determine the evolutionary relationship between MGP and BGP. Thirteen cDNAs and genes were cloned using standard methods or reconstructed through the use of comparative genomics and data mining. These sequences were compared with available annotated sequences (a total of 48 complete or nearly complete sequences, 28 BGPs and 20 MGPs) have been identified across 32 different species (representing most classes of vertebrates), and evolutionarily conserved features in both MGP and BGP were analyzed using bioinformatic tools and the Tree-Puzzle software. We propose that: 1) MGP and BGP genes originated from two genome duplications that occurred around 500 and 400 million years ago before jawless and jawed fish evolved, respectively; 2) MGP appeared first concomitantly with the emergence of cartilaginous structures, and BGP appeared thereafter along with bony structures; and 3) BGP derives from MGP. We also propose a highly specific pattern definition for the Gla domain of BGP and MGP.
An ideal goal of oral-craniofacial dental reconstructive therapy is to establish treatment modalities that predictably restore functional tissues. One major area of focus has been in the area of dental materials with marked improvements in the design of materials used to restore teeth/periodontium/bone lost as a consequence of disease or disorders. With advances in understanding the cell and molecular controls for development and regeneration of tooth structures, it is now possible to consider therapies that promote regeneration of lost tissues, along with replacement of these tissues. This review presents a background on our current knowledge as to the composition of the tooth/periodontium followed by a discussion on successes to date, both in vitro and in vivo, toward regenerating a whole tooth and next steps required to regenerate a functional tooth.
Atraumatic fractures of the skeleton in osteoporotic patients are directly related to a deterioration of bone strength. However, the failure of the bone tissue to withstand functional load bearing cannot be explained as a simple decrease in bone mineral density (quantity); strength is also significantly dependent upon bone quality. While a formal definition of bone quality is somewhat elusive, at the very least, it incorporates architectural, physical, and biologic factors that are critical to bone strength. Such factors include bone morphology (ie, trabecular connectivity, cross-sectional geometry, longitudinal curvature); the tissue's material properties (eg, stiffness, strength); its chemical composition and architecture (eg, ratio of calcium to other components of the organic and/or inorganic phase, collagen orientation, porosity, permeability); and the viability of the tissue (eg, responsivity of the bone cell population). Combining high-resolution structural indices of bone, as determined by micro-computed tomography; material properties determined by nanoindentation; and the chemical make-up of bone, as determined by infrared spectroscopy, helps to provide critical information toward a more comprehensive assessment of the interdependence of bone quality, quantity, and fracture risk.
The COLIA1 gene is a strong candidate for susceptibility to osteoporosis. The causal genetic variants are currently unclear, but the most likely are functional polymorphisms in the promoter and intron 1 of COLIA1.
The objective of the study was to determine whether promoter and intron 1 polymorphisms of COLIA1 or haplotypes defined by these polymorphisms regulate bone mineral density (BMD) in women.
This was a population-based association study involving 3270 women from the United Kingdom who took part in a regional osteoporosis screening program.
BMD at the lumbar spine (LS-BMD) and femoral neck (FN-BMD) was measured on two occasions approximately 6 yr apart, in relation to polymorphisms and haplotypes defined by polymorphisms within the COLIA1 intron 1 (+1245G/T; rs1800012) and promoter (-1997G/T; rs1107946; -1663IndelT; rs2412298).
The polymorphisms were in strong linkage disequilibrium, and three haplotypes accounted for more than 95% of alleles at the COLIA1 locus. The individual polymorphisms were associated with BMD, but the most consistent associations were with haplotypes defined by all three polymorphisms. Homozygote carriers of haplotype 2 (-1997G/-1663delT/+1245T) had reduced BMD at baseline (P = 0.007 for LS-BMD; P = 0.008 for FN-BMD), whereas homozygotes for haplotype 3 (-1997T/-1663insT/+1245G) had increased BMD (P = 0.007 for LS-BMD). Similar associations were observed at follow-up for haplotype 3, but the association with haplotype 2 was weaker due to increased uptake of hormone replacement therapy in homozygotes for this haplotype.
Two haplotypes defined by polymorphisms in the 5' flank of the COLIA1 regulate BMD in a bidirectional manner in women.
Acidic proteins play an important role during mineral formation in biological systems, but the mechanism of mineral formation is far from understood. In this paper, we report on the relationship between the structure of a protein and hydroxyapatite deposition under biomimetic conditions. Sericin, a type of silk protein, was adopted as a suitable protein for studying structural effect on hydroxyapatite deposition, since it forms a hydroxyapatite layer on its surface in a metastable calcium phosphate solution, and its structure has been reported. Sericin effectively induced hydroxyapatite nucleation when it has high molecular weight and a beta sheet structure. This indicates that the specific structure of a protein can effectively induce heterogeneous nucleation of hydroxyapatite in a biomimetic solution, i.e. a metastable calcium phosphate solution. This finding is useful in understanding biomineralization, as well as for the design of organic polymers that can effectively induce hydroxyapatite nucleation.
Extracellular matrix proteins control the formation of the inorganic component of hard tissues including bone, dentin, and enamel. The structural proteins expressed primarily in the enamel matrix are amelogenin, ameloblastin, enamelin, and amelotin. Other proteins, like biglycan, are also present in the enamel matrix as well as in other mineralizing and nonmineralizing tissues of mammals. In addition, the presence of sulfated enamel proteins, and "tuft" proteins has been examined and discussed in relation to enamel formation. The structural proteins of the enamel matrix must have specific protein-protein interactions to produce a matrix capable of directing the highly ordered structure of the enamel crystallites. Protein-protein interactions are also likely to occur between the secreted enamel proteins and the plasma membrane of the enamel producing cells, the ameloblasts. Such protein-protein interactions are hypothesized to influence the secretion of enamel proteins, establish short-term order of the forming matrix, and to mediate feedback signals to the transcriptional machinery of these cells. Membrane-bound proteins identified in ameloblasts, and which interact with the structural enamel proteins, include Cd63 (cluster of differentiation 63 antigen), annexin A2 (Anxa2), and lysosomal-associated glycoprotein 1 (Lamp1). These and related data help explain the molecular and cellular mechanisms responsible for the removal of the organic enamel matrix during the events of enamel mineralization, and how the enamel matrix influences its own fate through signaling initiated at the cell surface. The knowledge gained from enamel developmental studies may lead to better dental and nondental materials, or materials inspired by Nature. These data will be critical to scientists, engineers, and dentists in their pursuits to regenerate an entire tooth. For tooth regeneration to become a reality, the protein-protein interactions involving the key dental proteins must be identified and understood. The scope of this review is to discuss the current understanding of protein-protein interactions of the developing enamel matrix, and relate this knowledge to enamel biomineralization.
Hypophosphatemia is a genetically heterogeneous disease. Here, we mapped an autosomal recessive form (designated ARHP) to chromosome 4q21 and identified homozygous mutations in DMP1 (dentin matrix protein 1), which encodes a non-collagenous bone matrix protein expressed in osteoblasts and osteocytes. Intact plasma levels of the phosphaturic protein FGF23 were clearly elevated in two of four affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels and suggesting that DMP1 may regulate FGF23 expression.
The osteocyte, a terminally differentiated cell comprising 90%-95% of all bone cells, may have multiple functions, including acting as a mechanosensor in bone (re)modeling. Dentin matrix protein 1 (encoded by DMP1) is highly expressed in osteocytes and, when deleted in mice, results in a hypomineralized bone phenotype. We investigated the potential for this gene not only to direct skeletal mineralization but also to regulate phosphate (P(i)) homeostasis. Both Dmp1-null mice and individuals with a newly identified disorder, autosomal recessive hypophosphatemic rickets, manifest rickets and osteomalacia with isolated renal phosphate-wasting associated with elevated fibroblast growth factor 23 (FGF23) levels and normocalciuria. Mutational analyses showed that autosomal recessive hypophosphatemic rickets family carried a mutation affecting the DMP1 start codon, and a second family carried a 7-bp deletion disrupting the highly conserved DMP1 C terminus. Mechanistic studies using Dmp1-null mice demonstrated that absence of DMP1 results in defective osteocyte maturation and increased FGF23 expression, leading to pathological changes in bone mineralization. Our findings suggest a bone-renal axis that is central to guiding proper mineral metabolism.
Bone formation and development is a dynamic process involving a series of precisely controlled, distinct, cellular and biochemical events. As bone matures, stage-specific, sequentially expressed bone matrix proteins and hydroxyapatite mineral crystals become incorporated into a collagen fibril-based infrastructure, leading to an organized, stabilized, mineralized matrix. Consequently, this final functional structure contains a variety of matrix proteins present in differential amounts. These include proteins containing: a) glycosaminoglycan (GAG)-bearing proteins - aggrecan, versican, decorin, biglycan, fibromodulin, etc., as well as the free GAG, hyaluronic acid. b) glycoproteins - alkaline phosphatase, osteonectin, tetranectin, thrombospondin (TSP), fibronectin, vitronectin, osteopontin, bone sialoprotein, bone acidic glycoprotein, fibrillin, and tenascin, c) γ-carboxy glutamic acid (Gla)-containing proteins - osteocalcin, and matrix Gla protein (MGP), and d) other proteins - proteolipids, collagen-degrading metalloproteinases and their inhibitors, bone morphogenetic proteins, growth factors, serum-derived proteins, and cell-binding proteins. Emerging new technologies in cell biology, mineral analyses, and transgenic and knockout models are defining the critical proteins and requirements for physiological mineralization.
Kidney stones are aggregates of microcrystals, most commonly containing calcium oxalate monohydrate (COM) as the primary constituent. The formation of these aggregates in the renal tubules of the kidney and their attachment to epithelial cells lining the renal tubules are thought to involve adhesion events between COM crystal surfaces and urinary species that bind to these surfaces. The pathological behavior of COM is in stark contrast to calcium oxalate dihydrate (COD), a different mineral phase commonly found in voided urine but much less frequently in stones, and whose presence is thought to protect against stone formation. This observation suggests that the structure and composition of calcium oxalate crystal surfaces and the fundamental interactions of these surfaces with urinary species are crucial to unraveling the complex pathology of this debilitating disease.
In summary, we re-emphasize that experimental or theoretical considerations based on the study of geogenic apatites and of apatites synthesized in vitro inorganically or even in the presence of organic compounds, cannot be directly applied to the nanocrystals of the Ca-Pi phase of bone nanocrystals that grow and change in vivo under strict cellular control.
X-ray diffraction radial distribution function analysis was used to determine if a significant amount of an amorphous solid
phase of calcium phosphate exists in bone, and if so, whether the amount varies as a function of age and maturation. Unfractionated
cortical bone from embryonic and posthatch chicks of various ages and a low-density fraction of embryonic bone were studied.
No evidence was found for the presence of an amorphous solid phase of calcium phosphate in any of the samples studied, including
the recently deposited bone mineral of the low density fraction of embryonic bone. As little as 12.5% of synthetic amorphous
calcium phosphate (ACP) added to bone was readily detected by the radial distribution function technique used. The results
clearly indicate that the concept that ACP is the initial solid mineral phase deposited in bone, and the major mineral constituent
of young bone is no longer tenable. The concept does not provide an accurate description of the nature of the initial bone
mineral deposited, or the changes that occur with maturation, nor can it acount for the compositional and X-ray diffraction
changes that the mineral component undergoes during maturation and aging.
There is a need for new materials that can stimulate the body's own regenerative mechanisms and heal tissues. Porous templates
(scaffolds) are thought to be required for three-dimensional tissue growth. This article discusses bone regeneration and the
specifications of an ideal scaffold and the materials that may be suitable. Bioactive glasses have high potential as scaffold
materials as they stimulate bone cells to produce new bone, they are degradable in the body and they bond to bone. The two
types of bioactive glasses, their mechanisms for bioactivity and their potential for scaffold production are reviewed. Examples
of their current clinical use are highlighted.
The skeletons of adult echinoderms comprise large single crystals of calcite with smooth convoluted fenestrated morphologies,
raising many questions about how they form. By using water etching, infrared spectroscopy, electron diffraction, and environmental
scanning electron microscopy, we show that sea urchin spine regeneration proceeds via the initial deposition of amorphous
calcium carbonate. Because most echinoderms produce the same type of skeletal material, they probably all use this same mechanism.
Deposition of transient amorphous phases as a strategy for producing single crystals with complex morphology may have interesting
implications for the development of sophisticated materials.
Clear 3/8'' Lucite rod models at a scale of 1'' = D (the native-type period), and using four different colored ribbon markers to indicate one set of 'equivalent bands' in the SLS band pattern, clearly show the possible distribution of 'holes' and staining loci in native-type fibrils. Close-packed ordered arrays of the 4.4'' long rods (based on the Hodge-Petruska model) in which nearest neighbors are systematically staggered by D must have ordered distributions of the 0.6D long 'holes'. In one of the two simplest cases, holes occur singly, and are separated laterally by two molecular diameters. In the other case, contiguous holes form transversely continuous channels or slots within the fibril. Electron micrographs of both fish bone and embryonic chick bone clearly show that at least the initial mineralization is intrafibrillar in these systems.
Samples of decalcified chicken bone together with varying concentrations of phosphoproteins from bone or egg yolk (phosvitin) were used in vitro as heterogenous nucleators for the induction of Ca-P apatite crystals. The lag time between exposure of the collagen-phosphoprotein complexes and the time nucleation of crystals occurred decreased as the concentration of Ser(P) and Thr(P) increased. Enzymatic cleavage of the phosphate groups by wheat germ and phosphatase reversed this effort, indicating that the phosphate group per se principally facilitated the nucleation of Ca-P crystals by the phosphoprotein complex and collagen.
The infrared and Raman spectroscopy of bone and teeth tissues are reviewed. Characteristic spectra are obtained for both the mineral and protein components of these tissues. Vibrational spectroscopy is used to study the mineralization process, to define the chemical structure changes accompanying bone diseases, and to characterize interactions between prosthetic implants and tissues. Microspectroscopy allows acquisition of spatially resolved spectra, with micron scale resolution. Recently developed imaging modalities allow tissue imaging with chemical composition contrast.
During the secretory stage of enamel development, the hydroxyapatite crystals appear as thin ribbons which grow substantially in width and thickness during the later maturation stage. In this study, the atomic force microscope (AFM) was used to investigate developmentally-related changes in deproteinized enamel crystal surface topography in normal animals and in those receiving daily doses of fluoride. The AFM revealed previously undescribed surfaces features, some of which may represent growth sites or different crystalline phases. Secretory stage crystals had greater surface rugosity and were more irregular, with spherical sub-structures of 20-30 nm diameter arranged along the "c"-axis. Maturation stage crystals were smoother and larger but revealed both subnanometer steps and lateral grooves running parallel to the "c"-axis. Crystals from fluorotic tissue showed similar features but were more irregular with a higher degree of surface roughness, suggesting abnormal growth. The AFM may prove an important adjunct in determination of the mechanisms controlling crystal size and morphology in skeletal tissues.
This review examines recent advances in the analysis of genetic determinants of bone mass. It addresses both human and animal linkage studies as well as genetic manipulations in animals, inbred mouse models, and candidate gene analyses.
Recent studies have implicated novel regulatory pathways in bone biology including both the neuroendocrine system and metabolic pathways linked to lipid metabolism. Variations in the lipoprotein receptor-related protein 5 (LRP5), part of the Wnt-frizzled pathway, were independently identified by linkage in high and low bone mass families. Subsequently, other high bone mass syndromes have been shown to have mutations in this gene. Neural studies have shown the skeletal regulatory activity of leptin and neuropeptide Y receptors via the hypothalamus. Subsequently, the beta-adrenergic pathway has been implicated, with important changes in bone mass. The lipoxygenase 12/15 pathway, identified through inbred mouse models and through pharmacologic studies with specific inhibitors, has also been shown to have important effects on bone mass. These studies exemplify the value of genetic models both to identify and then confirm pathways by mutational study and pharmacologic interventions. Continuing candidate gene studies often performed with multiple loci complement such discoveries. However, these studies have not focused on the clinical endpoint of fracture and few have included large enough groups to engender confidence in the associations reported, as such studies may require thousands of individuals. Interestingly, results often differ by ethnicity, age, or gender. A small proportion have examined whether relevant genes influence response to treatment.
The combinations of human and animal genetic linkage studies have advanced understanding of the regulation of bone mass. Studies ranging from linkage to pharmacology provide optimism for new targets and treatments for osteoporosis.
Extracellular matrix metabolism plays a central role in development of skeletal tissues and in most orthopaedic diseases and trauma such as fracture or osteotomy repair, arthritis, cartilage repair, and congenital skeletal deformity. During development or disease, specific genes must be expressed in order to make or repair appropriate extracellular matrix. For example, specific gene expression patterns are characteristic of bone and cartilage. The precise expression pattern depends on a balance of positive and negative transcription factors, proteins that control the synthesis of mRNA from the specific gene. In cartilage, a number of studies indicate that Sox transcription factors are critical positive regulators in genes such as COL2A1, COL9A2, COL11A2, aggrecan, and CD-RAP. In addition, negative regulators are also essential to fine tune gene regulation in chondrocytes and to turn off gene expression in noncartilaginous tissues. Negative transcription factors in cartilage include partial differentialEF-1, snail/slug, CYRBP1, NT2, and C/EBP. Runx2 and osterix are critical transcription factors for osteogenesis but also have some influence on chondrogenesis. The availability of cis-regulatory sites in specific genes combined with the availability of transcription factors in the nucleus determines the level of gene expression.
Embryonic skeletal development involves the recruitment, commitment, differentiation, and maturation of mesenchymal cells into those in the skeletal tissue lineage, specifically cartilage and bone along the intramembranous and endochondral ossification pathways. The exquisite control of skeletal development is regulated at the level of gene transcription, cellular signaling, cell-cell and cell-matrix interactions, as well as systemic modulation. Mediators include transcription factors, growth factors, cytokines, metabolites, hormones, and environmentally derived influences. Understanding the mechanisms underlying developmental skeletogenesis is crucial to harnessing the inherent regenerative potential of skeletal tissues for wound healing and repair, as well as for functional skeletal tissue engineering. In this review, a number of key issues are discussed concerning the current and future challenges of the scientific investigation of developmental skeletogenesis in the embryo, specifically limb cartilage development, and how these challenges relate to regenerative or reparative skeletogenesis in the adult. Specifically, a more complete understanding the biology of skeletogenic progenitor cells and the cellular and molecular mechanisms governing tissue patterning and morphogenesis should greatly facilitate the development of regenerative approaches to cartilage repair.
Osteomalacia is a pathological bone condition in which there is deficient primary mineralization of the matrix, leading to an accumulation of osteoid tissue and reduced bone mechanical strength. The hypothesis that there are no qualitative or quantitative differences in osteomalacic bone mineral or matrix compared to disease-free bones was tested by examining unstained sections of polymethyl methacrylate (PMMA) embedded iliac crest biopsies using Fourier transform infrared imaging (FTIRI) at approximately 6-microm spatial resolution. Controls were seven female subjects, aged 36-57, without apparent bone disease. The experimental group consisted of 11 patients aged 22-72, diagnosed with osteomalacia. The spectroscopic parameters analyzed in each data set were previously established as sensitive to bone quality: phosphate/amide I band area ratio (mineral content), 1660/1690 cm(-1) peak ratio (collagen cross-links), and the 1030/1020 cm(-1) peak ratio (mineral crystallinity). The correspondence between spectroscopic mineral content (phosphate/amide I ratio) and ash weight was validated for apatite crystals of different composition and crystallite size. The FTIRI results from the biopsies expressed as color-coded images and pixel population means were compared with the nonparametric Mann-Whitney U test. There were no significant differences in the cortical parameters. Significant difference was found in the mineral content of the trabecular regions with a lower mean value in osteomalacia (P = 0.01) than in controls. Mineral crystallinity tended to be decreased in the trabecular bone (P = 0.09). This study supports the hypothesis that, in osteomalacia, the quality of the organic matrix and of mineral in the center of bone does not change, while less-than-optimal mineralization occurs at the bone surface. This study provides the first spectroscopic evaluation of whole bone mineral and matrix properties in osteomalacia, demonstrating that there are few differences in collagen cross-links between biopsies from patients with osteomalacia and from individuals without histological evidence of bone disease.
Several proteins associated with mineralised tissue (teeth and bone) or involved in calcium phosphate stabilisation in the body fluids, milk and saliva have been mapped to the q arm of human chromosome 4. These include the dentine/bone proteins dentine sialophosphoprotein (DSPP), dentine matrix protein 1 (DMP1), bone sialoprotein (BSP), matrix extracellular phosphoglycoprotein, osteopontin (OPN), enamelin, ameloblastin, milk caseins, salivary statherin, and proline-rich proteins. The proposed function of those that are multiphosphorylated is: (i) the stabilisation of calcium phosphate in solution (e.g. casein, statherin) preventing spontaneous precipitation and seeded-crystal growth or (ii) promoting biomineralisation (e.g. the phosphophoryn domain of DSPP), where the protein described as a template macromolecule, is proposed to act as a nucleator/promoter of crystal growth. The genes of these proteins have been subjected to conserved chromosomal synteny during mammalian evolution. The multiphosphorylated proteins statherin, caseins, phosphophoryn, BSP and OPN have been characterised as intrinsically disordered. The codon usage patterns for the amino acid serine reveal a bias for AGC and AGT codons within the human genes dspp, dmp1 and bsp, mouse dspp and dmp1 but not significantly for statherin or caseins. This pattern was also observed in the gene encoding hen phosvitin that also contains stretches of multiphosphorylated serines and in the dmp1 gene sequences of mammalian, reptilian and avian classes. In conclusion, these intrinsically disordered multiphosphorylated proteins are the translation products of genes displaying examples of codon usage bias, internal repeats and conserved chromosomal synteny within the mammalian class.
The role of DMP1 in mineralization was analyzed by comparing bone mineral and matrix properties in dmp1-null female mice to heterozygous and wildtype controls by FTIR imaging spectroscopy. The observed decreased mineral content in dmp1 null mice indicates a key role for dmp1 in bone mineralization. Indirect effects of DMP1 on other systems also determine the KO phenotype.
Dentin matrix protein 1 (DMP1), an acidic phosphorylated extracellular matrix protein, is highly expressed in mineralized tissues. In vitro, DMP1 peptides can promote or inhibit mineralization depending on the extent of phosphorylation, the peptide size, and concentration. To clarify the biological function of DMP1 protein on in vivo mineralization, this study analyzed bone properties of dmp1 knockout (KO) mice compared with heterozygous (HET) and wildtype (WT) controls.
Tibias from dmp1 KO and age-, sex-, and background-matched HET and WT mice at 4 and 16 weeks (N(total) = 60) were examined by Fourier transform infrared imaging (FTIRI), histology (n = 6 per genotype and age; N = 36), and geometry by muCT (n = 4 per genotype and age; N = 24). Serum ionic calcium and phosphate concentrations were also determined.
The mineral-to-matrix ratios (spectroscopic parameter of relative mineral content) were significantly lower in dmp1 KO mice tibias compared with WT and HET at 4 and 16 weeks. The mineral crystallinity (crystal size/perfection) was significantly increased in dmp1 KO and HET mice relative to WT. Collagen cross-link ratios (a spectroscopic parameter related to the relative amounts of nonreducible/reducible collagen cross-links) in dmp1 KO were not significantly different from WT and HET. Based on muCT, cortical bone cross-sectional areas at 16 but not 4 weeks were significantly reduced in the KO compared with controls. Maximum, minimum, and polar cross-sectional moments of inertia were significantly lower in dmp1 KO than in HET at 16 weeks but not at 4 weeks. Histological analysis and muCT 3-D images suggested that dmp1 KO mice had osteomalacia. Dmp1 KO mice had significantly lower ionic calcium and phosphate concentrations relative to WT, whereas in the HET, values for phosphate were equivalent, and calcium values were decreased relative to WT values.
The findings of decreased mineral-to-matrix ratio and increased crystal size in bones of dmp1 KO mice suggest that DMP1 has multiple roles (both direct and indirect) in the regulation of postnatal mineralization. We suggest that direct effects on mineral formation, crystal growth, and indirect effects on regulation of Ca x P concentrations and matrix turnover all contribute to the dominant phenotype in the dmp1 KO mouse.
Nanocrystalline hydroxyapatite (HAp) prepared by a precipitation route was investigated. The X-ray diffraction (XRD) powder patterns of the elongated nanocrystals with a typical diameter of about 10 nm and length of 30-50 nm (by transmission electron microscopy (TEM)) revealed the presence of HAp with significantly broadened XRD reflections. However, Ca deficiency was found, as the Ca/P ratio was 1.5 only (so-called calcium-deficient hydroxyapatite (CDHA)), and not 1.67. This Ca deficiency of nanocrystalline HAp is explained using NMR. It is shown unambiguously that (i) the nanocrystals consist of a crystalline core and a (disordered) surface region with a relative phosphate content of about 1:1, (ii) the crystalline core is HAp, and (iii) the surface region is dominated by hydrogen phosphate anions (with no hydroxyapatite-like structural motif) and structural water (hydrate). From the relative phosphate content and taking into account the crystal shape, the thickness of the surface layer along the main crystal axis could be estimated to be about 1 nm, and the average chemical composition of the surface layer has been determined. Finally, a Ca/P ratio of 1.52 was estimated from the NMR data that compares well with the value of 1.51 from chemical analysis. The important consequences are that the surface of nanocrystalline HAp has nothing in common with the bulk composition and that the chemistry of such materials (e.g. the binding of protein molecules to phosphate surfaces) must be reconsidered.
Adynamic or aplastic bone remains an important medical issue in children with chronic renal failure. To prevent the development of adynamic bone during treatment of secondary hyperparathyroidism, clinical recommendations have been made to maintain intact PTH levels at 2 to 4 times the normal values, avoid hypercalcemia, and keep serum phosphorus levels within age-appropriate limits in children with chronic renal failure. Less-calcemic vitamin D analogs and calcium-free and aluminum-free phosphate-binding agents should be used in children who can tolerate these agents. It is important to remember to reduce or discontinue any medication, whether it is vitamin D, a calcium salt, or any other agent that significantly lowers PTH, especially when intact PTH levels decline rapidly (to < 150 pg/mL) and serum calcium levels are higher than 10 mg/dL.
The strategy in biomineralization of initially depositing a less ordered mineral and then transforming it into a more crystalline mature phase is probably widespread among invertebrates. The report in this issue by N.J. Crane, V. Popescu, M.D. Morris, P. Steenhuis, M.A. Ignelzi, Raman spectroscopic evidence for octacalcium phosphate and other mineral species deposited during intramembraneous mineralization. Bone (In press), using micro-Raman spectroscopy to study early mineral deposits in mice calvaria, provides strong evidence that the transient precursor strategy also occurs in vertebrates.
Structural hierarchies are common in biologic systems and are particularly evident in biomineralized structures. In the craniofacial complex and skeleton of vertebrates, extracellular matrix and mineral of bone are structurally ordered at many dimensional scales from the macro level to the nano level. Indeed, the nanocomposite texture of bone, with nanocrystals of apatitic mineral embedded within a crosslinked matrix of fibrillar and nonfibrillar proteins, imparts to bone the very mechanical properties and toughness it needs to function in vital organ protection, musculoskeletal movement and mastication. This article focuses on how hierarchies of extracellular matrix protein organization influence bone cell behavior, tissue architecture and mineralization. Additional attention is given to recent work on the molecular determinants of mineral induction in bone, and how the mineralization process is subsequently regulated by inhibitory proteins.
Hydroxyapatite mineral is deposited in an organized fashion in the matrices of bones and teeth. The amount of mineral present, the composition of the mineral, and the size of the mineral crystals varies with both tissue and animal age, diet, health status, and the tissue being examined. Here, we review methods for measuring these differences in mineral properties and provide some illustrations from bones and teeth of animals in which the small leucine-rich proteoglycans (biglycan and decorin) were ablated. Differences in mineral properties between biglycan-deficient bones and teeth are related to the functions of this small proteoglycan in these tissues.
The resistance of bone to fracture is determined by its geometric and material properties. The geometry and density can be determined by radiographic methods, but material properties such as collagen structure, mineral composition, and crystal structure currently require analysis by invasive techniques. Backscatter electron imaging provides quantitative information on the distribution of the mineral within tissue sections, and infrared and other vibrational spectroscopic methods can supplement these data, providing site-specific information on mineral content as well as information on collagen maturity and distributions of crystal size and composition. This information contributes to the knowledge of "bone quality."
Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and increased risk of fragility fractures. Twin and family studies have shown that the heritability of bone mineral density (BMD) and other determinants of fracture risk-such as ultrasound properties of bone, skeletal geometry, and bone turnover-is high, although heritability of fracture is modest. Many different genetic variants of modest effect size are likely to contribute to the regulation of these phenotypes by interacting with environmental factors such as diet and exercise. Linkage studies in rare Mendelian bone diseases have identified several previously unknown genes that play key roles in regulating bone mass and bone turnover. In many instances, subtle polymorphisms in these genes have also been found to regulate BMD in the general population. Although there has been extensive progress in identifying the genetic variants that regulate susceptibility to osteoporosis, most of the genes and genetic variants that regulate bone mass and susceptibility to osteoporosis remain to be discovered.
Recent advances in biology, medicine, and engineering have led to the discovery of new therapeutic
agents and novel materials for the repair of large bone defects caused by trauma, congenital defects, or
bone tumors. These repair strategies often utilize degradable polymeric scaffolds for the controlled localized
delivery of bioactive molecules to stimulate bone ingrowth as the scaffold degrades. Polymer composition,
hydrophobicity, crystallinity, and degradability will affect the rate of drug release from these scaffolds,
as well as the rate of tissue ingrowth. Accordingly, this chapter examines the wide range of synthetic
degradable polymers utilized for osteogenic drug delivery. Additionally, the therapeutic proteins involved
in bone formation and in the stimulation of osteoblasts, osteoclasts, and progenitor cells are reviewed
to direct attention to the many critical issues influencing effective scaffold design for bone repair.
In this study the changes in properties of the maturing mantle and circumpulpal dentin were quantitatively analyzed. Sections from six fetal bovine undecalcified incisors were used. Regions of mantle and circumpulpal dentin of sequential maturation stages were identified on spectroscopic images acquired by Fourier Transform Infrared Imaging. Spectroscopic parameters corresponding to mineral properties at these stages were analyzed and reported as a function of distance from the cervix of the incisor, the latter representing tissue age. Mineral parameters were correlated with distance from the cervix. Values of these parameters in mantle and circumpulpal dentin were compared. A multi-phasic pattern of changes was found for all the parameters examined, with most of the alterations occurring in the initial maturation period. The patterns of temporal variation in mantle and circumpulpal dentin mineral properties show distinct developmental stages and were not identical for the two dentin compartments. The study showed that mineral maturation in dentin is not a linear process and that mantle dentin is developmentally distinct from circumpulpal dentin, presenting at certain stages different physicochemical events during the maturation of the tissue.