[Show abstract][Hide abstract] ABSTRACT: Autozygosity mapping and clonal sequencing of an Omani family identified mutations in the uncharacterized gene, C4orf26, as a cause of recessive hypomineralized amelogenesis imperfecta (AI), a disease in which the formation of tooth enamel fails. Screening of a panel of 57 autosomal-recessive AI-affected families identified eight further families with loss-of-function mutations in C4orf26. C4orf26 encodes a putative extracellular matrix acidic phosphoprotein expressed in the enamel organ. A mineral nucleation assay showed that the protein's phosphorylated C terminus has the capacity to promote nucleation of hydroxyapatite, suggesting a possible function in enamel mineralization during amelogenesis.
Full-text · Article · Aug 2012 · The American Journal of Human Genetics
[Show abstract][Hide abstract] ABSTRACT: In this article, the authors present evidence-based clinical recommendations regarding the use of nonfluoride caries preventive agents. The recommendations were developed by an expert panel convened by the American Dental Association (ADA)Council on Scientific Affairs. The panel addressed several questions regarding the efficacy of nonfluoride agents in reducing the incidence of caries and arresting or reversing the progression of caries.
A panel of experts convened by the ADA Council on Scientific Affairs, in collaboration with ADA Division of Science staff, conducted a MEDLINE search to identify all randomized and nonrandomized clinical studies regarding the use of non fluoride caries-preventive agents.
The panel reviewed evidence from 50 randomized controlled trials and 15 nonrandomized studies to assess the efficacy of various nonfluoride caries-preventive agents.
The panel concluded that certain nonfluoride agents may provide some benefit as adjunctive therapies in children and adults at higher risk of developing caries. These recommendations are presented as a resource for dentists to consider in the clinical decision-making process. As part of the evidence based approach to care, these clinical recommendations should be integrated with the practitioner’s professional judgment and the patient’s needs and preferences.
Full-text · Article · Sep 2011 · Journal of the American Dental Association (1939)
[Show abstract][Hide abstract] ABSTRACT: Transforming growth factor-beta1 (TGF-beta1) is a key regulator of many cellular processes, including cell adhesion, the immune response and synthesis of extracellular matrix proteins. In the present study, we report the characterization of enamel defects in a transgenic mouse model overexpressing TGF-beta1 in odontoblasts and ameloblasts, its expression being driven by the promoter sequences of the dentin sialophosphoprotein gene. As reported earlier, these mice develop distinct dentin defects similar to those seen in human dentin dysplasia and dentinogenesis imperfecta. A further detailed examination of enamel in these mice revealed that from the early secretory stage, ameloblasts began to detach from dentin to form cyst-like structures. A soft X-ray analysis revealed that this cyst-like structure had a disorganized and partially mineralized matrix with an abnormal mineralization pattern and a globular appearance. In the molars, the enamel was not only pitted and hypoplastic, but enamel rods were completely lost. Thus, altered TGF-beta1 expression in the tooth seems to trigger detachment of ameloblasts and abnormal secretion and deposition of minerals in the cyst-like structures adjoining the dentin. We speculate that the altered expression of TGF-beta1 in teeth impacts the adhesion process of ameloblasts to dentin.
No preview · Article · Jun 2006 · European Journal Of Oral Sciences
[Show abstract][Hide abstract] ABSTRACT: Kallikrein-4 is known to be highly expressed during the maturation stage of enamel formation and is thought to be critical for the final phase of crystallite growth. The purpose of this study was to evaluate the enamel phenotype in humans with a known KLK-4 mutation (g.2142G>A). Primary teeth from two individuals with a known KLK-4 mutation were evaluated using amino acid analysis and light and electron microscopy. Light microscopy showed the enamel was of normal thickness but opaque throughout its width compared with normal enamel. Electron microscopy showed enamel affected by the KLK-4 mutation had a normal prismatic structure and generally had a well-organized and discernable crystallite composition. In some areas, globular structures were present where crystallites were not discernable or appeared to have an altered morphology. The KLK-4 mutant enamel had an increased protein content compared with normal enamel. Human enamel formed with a lack of functioning KLK-4 proteinase is altered primarily in the completeness of crystallite growth, while enamel thickness and prism structure remains essentially normal. Collectively, these studies suggest that the KLK-4 proteinase is essential for the final crystallite growth of enamel but is not critical for crystallite orientation, prism formation or enamel thickness.
No preview · Article · May 2006 · European Journal Of Oral Sciences
[Show abstract][Hide abstract] ABSTRACT: The amelogenesis imperfectas (AI) are a diverse group of genetic disorders primarily affecting the quality and or quantity of enamel, however, affected individuals often have an open bite malocclusion. Three main AI types are recognized based on the perceived developmental mechanisms involved and the enamel phenotype. The purpose of this investigation was to evaluate the association of the AI enamel defect with craniofacial features characteristic of an open bite malocclusion. The sample consisted of 54 AI affected and 34 unaffected family members from 18 different kindreds. Lateral cephalograms were digitized and measurements evaluated for vertical plane alterations using Z-scores. Forty two percent of AI affected individuals and 12% of unaffected family members had dental or skeletal open bite malocclusions. Skeletal open bite malocclusion was variably expressed in AI affected individuals. The enamel phenotype severity did not necessarily correspond with the presence or severity of open bite malocclussion. Open bite malocclusion occurred in individuals with AI caused by mutations in the AMELX and ENAM genes even though these genes are considered to be predominantly or exclusively expressed in teeth. Affected AI individuals with cephalometric values meeting our criteria of skeletal open bite malocclusion were observed in all three major AI types. The pathophysiological relationship between AI associated enamel defects and open bite malocclusion remains unknown.
No preview · Article · Aug 2005 · Archives of Oral Biology
[Show abstract][Hide abstract] ABSTRACT: Amelogenins, major components of developing enamel, are predominantly involved in the formation of tooth enamel. Although amelogenins are also implicated in cementogenesis, their precise spatial expression pattern and molecular role are not clearly understood. Here, we report for the first time the expression of two alternate splice forms of amelogenins, M180 and the leucine-rich amelogenin peptide (LRAP), in the periodontal region of mouse tooth roots. Lack of M180 and LRAP mRNA expression correlated with cementum defects observed in the amelogenin-null mice. The cementum defects were characterized by an increased presence of multinucleated cells, osteoclasts, and cementicles. These defects were associated with an increased expression of the receptor activator of the nuclear factor-kappa B ligand (RANKL), a critical regulator of osteoclastogenesis. These findings indicate that the amelogenin splice variants, M180 and LRAP, are critical in preventing abnormal resorption of cementum.
Full-text · Article · Oct 2003 · Journal of Biological Chemistry
[Show abstract][Hide abstract] ABSTRACT: Dentin sialophosphoprotein (Dspp) is mainly expressed in teeth by the odontoblasts and preameloblasts. The Dspp mRNA is translated into a single protein, Dspp, and cleaved into two peptides, dentin sialoprotein and dentin phosphoprotein, that are localized within the dentin matrix. Recently, mutations in this gene were identified in human dentinogenesis imperfecta II (Online Mendelian Inheritance in Man (OMIM) accession number 125490) and in dentin dysplasia II (OMIM accession number 125420) syndromes. Herein, we report the generation of Dspp-null mice that develop tooth defects similar to human dentinogenesis imperfecta III with enlarged pulp chambers, increased width of predentin zone, hypomineralization, and pulp exposure. Electron microscopy revealed an irregular mineralization front and a lack of calcospherites coalescence in the dentin. Interestingly, the levels of biglycan and decorin, small leucine-rich proteoglycans, were increased in the widened predentin zone and in void spaces among the calcospherites in the dentin of null teeth. These enhanced levels correlate well with the defective regions in mineralization and further indicate that these molecules may adversely affect the dentin mineralization process by interfering with coalescence of calcospherites. Overall, our results identify a crucial role for Dspp in orchestrating the events essential during dentin mineralization, including potential regulation of proteoglycan levels.
Full-text · Article · Aug 2003 · Journal of Biological Chemistry
[Show abstract][Hide abstract] ABSTRACT: Transforming growth factor (TGF)-beta1 is expressed in developing tooth from the initiation stage through adulthood. Odontoblast-specific expression of TGF-beta1 in the tooth continues throughout life; however, the precise biological functions of this growth factor in the odontoblasts are not clearly understood. Herein, we describe the generation of transgenic mice that overexpress active TGF-beta1 predominantly in the odontoblasts. Teeth of these mice show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules. Dentin extracellular matrix components such as type I and III collagens are increased and deposited abnormally in the dental pulp, similar to the hereditary human tooth disorders such as dentin dysplasia and dentinogenesis imperfecta. Calcium, one of the crucial inorganic components of mineralization, is also apparently increased in the transgenic mouse teeth. Most importantly, the expression of dentin sialophosphoprotein (dspp), a candidate gene implicated in dentinogenesis imperfecta II (MIM 125420), is significantly down-regulated in the transgenic teeth. Our results provide in vivo evidence suggesting that TGF-beta1 mediated expression of dspp is crucial for dentin mineralization. These findings also provide for the first time a direct experimental evidence indicating that decreased dspp gene expression along with the other cellular changes in odontoblasts may result in human hereditary dental disorders like dentinogenesis imperfecta II (MIM 125420) and dentin dysplasia (MIM 125400 and 125420).
No preview · Article · May 2001 · Journal of Biological Chemistry
[Show abstract][Hide abstract] ABSTRACT: Oral health and systemic health are intimately related, and a thorough evaluation of the oral health of children is critical in providing appropriate health care. By understanding the normal sequence and patterns of tooth development, clinicians can readily identify children who deviate from normal dental development and provide appropriate interventions or make appropriate referrals. Developmental defects of the human dentition are not uncommon and can severely adversely affect the physical and psychological health of children. Despite the severity of some developmental defects of the dentition, the ability to diagnose and manage these conditions, in most cases, allows children the benefit of optimal oral health.
No preview · Article · Nov 2000 · Pediatric Clinics of North America
[Show abstract][Hide abstract] ABSTRACT: Amelogenesis imperfecta, a group of hereditary conditions primarily affecting the enamel, has been associated with dental anomalies, including taurodontism, congenitally missing teeth, delayed eruption, crown resorption, and abnormal enamel density. The purpose of this study was to assess the prevalence of these anomalies in an amelogenesis imperfecta population. The study group consisted of members of 9 unrelated families--22 family members with amelogenesis imperfecta and 13 unaffected family members. Panoramic radiographs were evaluated for taurodontism, congenitally missing teeth, delayed tooth eruption, pathologic dental resorption, pulp calcification, and radiographic enamel density. The prevalence of taurodontism was similar in people with amelogenesis imperfecta and normal people; all of the remaining parameters were more commonly observed in people with amelogenesis imperfecta. The radiographic enamel density was quantitatively reduced in teeth affected by amelogenesis imperfecta in comparison with teeth with normal enamel. These findings suggest that some of the features associated with amelogenesis imperfecta result from abnormal enamel formation (eg, decreased enamel density, crown resorption) whereas others may occur as a result of expression of the genetic mutation in cells other than ameloblasts (eg, abnormal eruption, pulp calcification).
No preview · Article · Oct 1999 · Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology
[Show abstract][Hide abstract] ABSTRACT: The development of human enamel involves a complex series of events including the secretion and degradation of a unique extracellular matrix. Ameloblasts progress through a succession of cellular phenotypes executing specialized secretory and regulatory functions. When performing optimally, ameloblasts produce a highly structured and mineralized tissue. Given the elaborate developmental events required for normal enamel formation, it is not surprising that a variety of enamel malformations arise from defects in matrix synthesis, secretion and extracellular processing. Normal matrix secretion and post-secretory processing by ameloblasts can be affected by a variety of hereditary and environmental conditions. These disturbances can result in an abnormal amount and/or composition of matrix proteins, and subsequently, an altered enamel structure and/or mineral content. For example, abnormal matrix removal during enamel maturation apparently contributes to hypomineralization associated with dental fluorosis. Incomplete matrix removal can also occur in several different forms of the hereditary condition amelogenesis imperfects. Specific types of this condition can have retention of substantial enamel protein (e.g. 5% by weight) that is, at least in part, composed of amelogenin and/or its breakdown products. Characterization of the enamel proteins in teeth affected by developmental disturbances can provide insight into the pathogenesis and normal formation of this highly specialized tissue.
No preview · Article · Feb 1997 · Ciba Foundation symposium
[Show abstract][Hide abstract] ABSTRACT: Tricho-dento-osseous syndrome (TDO) is characterized by abnormal bone, hair, and tooth morphology. However, the reported craniofacial abnormalities are not well characterized. The purpose of this study was to compare the craniofacial parameters of 25 subjects affected with TDO (A) with those of 15 unaffected relatives (U). Standardized lateral cephalograms were traced and digitized. Each subject's data were compared by age and sex to cephalometric standards (Bolton, Behrents); severity was scored by standard deviations from the standard mean, and then grouped into A vs. U. All cephalograms were evaluated for frontal sinuses, mastoid pneumatization, diploe, and bone density, and cranial thickness was measured. Cranial base length (SN; NBa), cranial base angle (BaSN), and mandibular body length (GoPg) were greater in A than in U (p < or = 0.05). Both groups had longer total and lower facial heights (NMe; ANSMe) compared with normal standards. Frontal sinuses, mastoid pneumatization and diploe were visible less often in A than in U (p < or = 0.05). Parietal bone and bone at lambda was significantly thicker (p < or = 0.05) in A than in U. Variability was substantial in many measures in both A and U. The major TDO craniofacial features involve the cranial base, mandibular body length, absence of visible pneumatized mastoids, frontal sinuses and diploe, and thicker cranial bone.
No preview · Article · Jan 1997 · Clinical Genetics
[Show abstract][Hide abstract] ABSTRACT: Tricho-dento-osseous syndrome is a rare autosomal dominant hereditary disorder characterized by curly hair, enamel hypoplasia, taurodont teeth, and thickened cortical bone. A large kindred with this syndrome has been identified in North Carolina and characterized by pedigree analysis and clinical evaluation. Hair samples (N = 3) and an exfoliated primary tooth (N = 1) from persons with tricho-dento-osseous syndrome and hair and teeth from unaffected persons were examined. Scanning electron microscopy showed that the hair shaft morphology, diameter, and cuticular pattern and periodicity were similar for the tricho-dento-osseous syndrome and control samples. The affected tooth was examined using light microscopy and a scanning electron microscope that showed pitting hypoplasia of the enamel surface, an extremely large pulp chamber, and dentin that appeared structurally normal. The affected enamel was uniformly thin, only 10% the thickness of the control enamel. The bulk of this enamel showed no prism formation. This study indicates that although hair with tricho-dento-osseous syndrome often is clinically curly, it can be straight, and it does not appear to have unique ultrastructural features that are of diagnostic benefit. The dental characteristics of tricho-dento-osseous syndrome were the most consistent feature seen in this kindred.
No preview · Article · Jun 1994 · Oral Surgery Oral Medicine Oral Pathology
[Show abstract][Hide abstract] ABSTRACT: X-linked amelogenesis imperfecta has been proven in a number of families to be linked to or involve a variety of mutations in the X chromosome amelogenin gene. The purpose of this study was to characterize the enamel ultrastructure and enamel protein in a kindred affected by X-linked amelogenesis imperfecta. Exfoliated primary teeth were obtained from two related persons (one male, one female) who had X-linked amelogenesis imperfecta with marked hypoplasia. Normal enamel (age and sex matched) was used as the control for all analyses. The teeth were evaluated using light microscopy, scanning electron microscopy, and microradiography. The enamel of the heterozygous female was hypoplastic and rough with marked surface depressions. Enamel beneath these depressions was poorly organized and lacked a prismatic structure. The affected male had very thin enamel (approximately 40 microns) that also lacked an organized structure. Enamel protein from the teeth of the heterozygous female and the control was characterized using amino acid analysis. The protein content of the enamel of the female with amelogenesis imperfecta was 0.40% (N = 1) whereas the control enamel ranged from 0.17% to 0.45% (N = 4; mean = 0.34%). This study indicates that although the enamel in both the male and female with X-linked amelogenesis imperfecta displayed marked structural abnormalities the enamel protein was similar in quantity and amino acid composition for normal and X-linked amelogenesis imperfecta (female) enamel.(ABSTRACT TRUNCATED AT 250 WORDS)
No preview · Article · Sep 1993 · Oral Surgery Oral Medicine Oral Pathology