Jose Granjeiro
Research interests
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Interestsbioengineering, Bone Biology, Biomaterials, Bone tissue engineering, Material Chemistry, Medical Nanotechnology, Nanobiotechnology, Nano Drug Delivery, Drug Delivery Systems, Nanomedicine, Nano Devices, Nanomaterials, Nanoparticles
Publications
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2.92Impact points
Periosteal-derived cells for bone bioengineering: a promising candidate.
Clinical oral implants research. 01/2012;
PURPOSE: Over the last years so many efforts have been made in order to indentify natural sources of osteogenic cells for the success of bone bioengineering. Among them, periosteum tissue has emerged as an interesting candidate. Thus, we decided to evaluate the osteogenic potential of periosteal-der... [more] PURPOSE: Over the last years so many efforts have been made in order to indentify natural sources of osteogenic cells for the success of bone bioengineering. Among them, periosteum tissue has emerged as an interesting candidate. Thus, we decided to evaluate the osteogenic potential of periosteal-derived cells by describing a sequence of biological events since initial morphological changes to mineralization of extracellular matrix (ECM). METHODS: Periosteal-derived cells were obtained from calvarial of adult rats. After the primary culture and expansion, the adherent cells were cultured at 7, 14, 21 and 28 days under a classical osteogenic culture medium in order to evaluate the differentiation of those cells in mature osteoblast. It was monitored by evaluating a time-line of alkaline phosphatase (ALP) activity (biomarker of osteoblast differentiation) and afterwards nodules of mineralization (measured by von Kossa staining and calcium content). RESULTS: Analysis from phase-contrast microscopy revealed mainly morphological changes ranging since fibroblast-shaped (7 days, semi-confluent culture at exponential growth) to polyhedral-shaped cells (14-28 days, confluent culture during differentiation process). ALP activity was linearly increased since 14-28 days while amount of protein remained unchanged. Interesting, our data from von Kossa staining reveled a highest incidence of mineralization nodules at 28 days. CONCLUSION: Taken our results together, we can suggest that periosteal-derived cells present an interesting potential to differentiate in mature osteoblast able to promote mineralization in vitro by incorporating to ECM circulating calcium from extracellular compartment. From our point of view, this source of osteogenic cells can be explored by bioengineers in order to advance therapeutic protocols able to solve bone degenerative lesions.
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1.96Impact points
The association of human primary bone cells with biphasic calcium phosphate (βTCP/HA 70:30) granules increases bone repair.
Journal of materials science. Materials in medicine. 12/2011;
This work evaluates the suitability of biphasic calcium phosphate (BCP) granules (β-TCP/HA 70:30) as potential carriers for cell-guided bone therapy. The BCP granules were obtained by synthesis in the presence of wax, thermal treatment, crushing and sieving and characterized by scanning electron mic... [more] This work evaluates the suitability of biphasic calcium phosphate (BCP) granules (β-TCP/HA 70:30) as potential carriers for cell-guided bone therapy. The BCP granules were obtained by synthesis in the presence of wax, thermal treatment, crushing and sieving and characterized by scanning electron microscopy (SEM), X-ray diffraction and Fourier transform infrared spectroscopy. The cytocompatibility of the BCP granules was confirmed by a multiparametric cytotoxicity assay. SEM analysis showed human bone cell adhesion and migration after seeding onto the material. Rat subcutaneous xenogeneic grafting of granules associated to human bone cells revealed a more accentuated moderate chronic inflammatory infiltrate, without signs of a strong xenoreactivity. Histomorphometrical analysis of bone repair of defects in rat skulls (∅ = 5 mm) has shown that bone cell associated-BCP and autograft promoted a two- and threefold increase, respectively, on new bone formation after 45 days, as compared to BCP alone and blood clot. The increase in bone repair supports the suitability the biocompatible (70:30) BCP granules as injectable and mouldable scaffolds for human cells in bone bioengineering.
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Unveiling novel genes upregulated by both rhBMP2 and rhBMP7 during early osteoblastic transdifferentiation of C2C12 cells.
BMC research notes. 09/2011; 4:370.
ABSTRACT: We set out to analyse the gene expression profile of pre-osteoblastic C2C12 cells during osteodifferentiation induced by both rhBMP2 and rhBMP7 using DNA microarrays. Induced and repressed genes were intercepted, resulting in 1,318 induced genes and 704 repressed genes by both rhBMP2 and r... [more] ABSTRACT: We set out to analyse the gene expression profile of pre-osteoblastic C2C12 cells during osteodifferentiation induced by both rhBMP2 and rhBMP7 using DNA microarrays. Induced and repressed genes were intercepted, resulting in 1,318 induced genes and 704 repressed genes by both rhBMP2 and rhBMP7. We selected and validated, by RT-qPCR, 24 genes which were upregulated by rhBMP2 and rhBMP7; of these, 13 are related to transcription (Runx2, Dlx1, Dlx2, Dlx5, Id1, Id2, Id3, Fkhr1, Osx, Hoxc8, Glis1, Glis3 and Cfdp1), four are associated with cell signalling pathways (Lrp6, Dvl1, Ecsit and PKCδ) and seven are associated with the extracellular matrix (Ltbp2, Grn, Postn, Plod1, BMP1, Htra1 and IGFBP-rP10). The novel identified genes include: Hoxc8, Glis1, Glis3, Ecsit, PKCδ, LrP6, Dvl1, Grn, BMP1, Ltbp2, Plod1, Htra1 and IGFBP-rP10. BMPs (bone morphogenetic proteins) are members of the TGFβ (transforming growth factor-β) super-family of proteins, which regulate growth and differentiation of different cell types in various tissues, and play a critical role in the differentiation of mesenchymal cells into osteoblasts. In particular, rhBMP2 and rhBMP7 promote osteoinduction in vitro and in vivo, and both proteins are therapeutically applied in orthopaedics and dentistry. Using DNA microarrays and RT-qPCR, we identified both previously known and novel genes which are upregulated by rhBMP2 and rhBMP7 during the onset of osteoblastic transdifferentiation of pre-myoblastic C2C12 cells. Subsequent studies of these genes in C2C12 and mesenchymal or pre-osteoblastic cells should reveal more details about their role during this type of cellular differentiation induced by BMP2 or BMP7. These studies are relevant to better understanding the molecular mechanisms underlying osteoblastic differentiation and bone repair.
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0.88Impact points
Prevalence of Dental Anomalies in Nonsyndromic Individuals With Cleft Lip and Palate: A Systematic Review and Meta-analysis.
The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. 07/2011; 49(2):194-200.
Objective : To assess whether individuals born with nonsyndromic oral clefts display a higher frequency of dental anomalies. Design : A search of MEDLINE, BIREME, OVID ALL EMB Reviews, and The Cochrane Library was conducted. The methodologic quality of the papers selected was assessed and scored. Pa... [more] Objective : To assess whether individuals born with nonsyndromic oral clefts display a higher frequency of dental anomalies. Design : A search of MEDLINE, BIREME, OVID ALL EMB Reviews, and The Cochrane Library was conducted. The methodologic quality of the papers selected was assessed and scored. Papers reporting observational controlled studies of nonsyndromic forms of oral cleft matched for dental anomalies in primary and/or permanent teeth were included without language restrictions. Eligible studies were scored as "A"-low risk of bias, "B"-moderate risk of bias, or "C"-high risk of bias and poor quality. Fixed and random effects models were used to aggregate individual odds ratios (OR) and to derive pooled estimates and 95% confidence intervals. Results : Six studies fulfilled our selection criteria and were included in the meta-analysis. Three distinct subgroup analyses were carried out in terms of dental anomalies. In the tooth agenesis meta-analysis, a random effects model was used because of heterogeneity and showed a significant association between tooth agenesis and oral clefts (OR = 12.31; 95% confidence interval [CI] = 3.75 to 40.36). In the remaining analyses, the fixed effects model revealed a positive association between supernumerary (OR = 4.99; 95% CI, 2.58 to 9.64) and crown morphologic abnormalities (OR = 5.69; 95% CI, 3.96 to 8.19) with oral clefts. Most included studies were of low to moderate quality. Conclusion : Although general limitations in study design were observed, the evidence suggests that a higher number of dental anomalies in the permanent dentition are noted in individuals born with oral clefts.
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0.88Impact points
CRISPLD2 Variants Including a C471T Silent Mutation May Contribute to Nonsyndromic Cleft Lip With or Without Cleft Palate.
The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. 07/2011; 48(4):363-70.
Objective : To assess the association between nonsyndromic (NS) cleft lip with or without cleft palate (CL(P)) and single-nucleotide polymorphisms (SNPs) within the CRISPLD2 gene (cysteine-rich secretory protein LCCL domain containing 2). Design : Four SNPs within the CRISPLD2 gene domain (rs1546124... [more] Objective : To assess the association between nonsyndromic (NS) cleft lip with or without cleft palate (CL(P)) and single-nucleotide polymorphisms (SNPs) within the CRISPLD2 gene (cysteine-rich secretory protein LCCL domain containing 2). Design : Four SNPs within the CRISPLD2 gene domain (rs1546124, rs8061351, rs2326398, rs4783099) were genotyped to test for association via family-based association methods. Participants : A total of 5826 individuals from 1331 families in which one or more family member is affected with CL(P). Results : Evidence of association was seen for SNP rs1546124 in U.S. (p = .02) and Brazilian (p = .04) Caucasian cohorts. We also found association of SNP rs1546124 with cleft palate alone (CP) in South Americans (Guatemala and ECLAMC) and combined Hispanics (Guatemala, ECLAMC, and Texas Hispanics; p = .03 for both comparisons) and with both cleft lip with cleft palate (CLP; p = .04) and CL(P) (p = .02) in North Americans. Strong evidence of association was found for SNP rs2326398 with CP in Asian populations (p = .003) and with CL(P) in Hispanics (p = .03) and also with bilateral CL(P) in Brazilians (p = .004). In Brazilians, SNP rs8061351 showed association with cleft subgroups incomplete CL(P) (p = .004) and unilateral incomplete CL(P) (p = .003). Prediction of SNP functionality revealed that the C allele in the C471T silent mutation (overrepresented in cases with CL(P) presents two putative exonic splicing enhancer motifs and creates a binding site AP-2 alpha, a transcription factor involved in craniofacial development. Conclusions : Our results support the hypothesis that variants in the CRISPLD2 gene may be involved in the etiology of NS CL(P).
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0.39Impact points
Hydroxyapatite crystallinity does not affect the repair of critical size bone defects.
Journal of applied oral science : revista FOB. 06/2011; 19(4):337-42.
The physicochemical properties of hydroxyapatite (HA) granules were observed to affect the biological behavior of graft materials. The aim of this work was to analyze the tissue response of two HA granules with different crystallinity and Ca/P ratio in vivo. The HA granules were produced in the Biom... [more] The physicochemical properties of hydroxyapatite (HA) granules were observed to affect the biological behavior of graft materials. The aim of this work was to analyze the tissue response of two HA granules with different crystallinity and Ca/P ratio in vivo. The HA granules were produced in the Biomaterials Laboratory (COPPE/UFRJ). The testing materials were HA granules presenting a Ca/P molar ratio of 1.60 and 28% crystallinity (HA-1), and a Ca/P molar ratio of 1.67 and 70% crystallinity (HA-2). Both HAs were implanted into a critical-size calvaria rat defects. To note, in the control group, the bone defects were filled with blood clot only. Descriptive and histomorphometric analyses after 1, 3, and 6 months postoperatively showed mild inflammatory infiltrate, mainly comprising macrophage-like and multinucleated giant cells, and an increase in the volume density of the fibrous tissues (p<0.05), which was in contrast to the similar volume density of the newly formed bone and biomaterials in relation to the control group. Thus, we concluded that HA-1 and HA-2 are biocompatible and non-degradable, and that crystallinity does not affect bone repair of critical size defects.
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2.60Impact points
Adsorption of chlorhexidine on synthetic hydroxyapatite and in vitro biological activity.
Colloids and surfaces. B, Biointerfaces. 05/2011; 87(2):310-8.
The kinetic of chlorhexidine digluconate (CHXDG) uptake from aqueous solution by hydroxyapatite (HA) was investigated by ultraviolet (UV) analysis performed in HA powder (UV-solid) after the CHX adsorption. Adsorption isotherm of chlorhexidine (CHX) uptake was modeled by a combination of Languimir a... [more] The kinetic of chlorhexidine digluconate (CHXDG) uptake from aqueous solution by hydroxyapatite (HA) was investigated by ultraviolet (UV) analysis performed in HA powder (UV-solid) after the CHX adsorption. Adsorption isotherm of chlorhexidine (CHX) uptake was modeled by a combination of Languimir and Langmuir-Freundlich mechanisms. Strong molecule-molecule interactions and positive cooperativity predominated in the surface when CHX concentration was above 8.6 μg(CHX)/mg(HA). UV-solid spectra (shape, intensity and band position) of CHX bound to HA revealed that long-range molecular structures, such as aggregates or micelles, started to be formed at low CHX concentrations (1.52 μg(CHX)/mg(HA)) and predominated at high concentrations. Grazing-incidence X-ray diffraction (GIXRD) analysis from synchrotron radiation discarded the formation of crystalline structures on HA surface or precipitation of CHX crystalline salts, as suggested in previous works. The effect of the HA/CHX association on HA in vitro bioactivity, cytotoxicity and CHX antimicrobial activity was evaluated. It was shown that CHX did not inhibit the precipitation of a poorly crystalline apatite at HA/CHX surface after soaking in simulating body fluid (SBF). Cell viability studies after exposure to extracts of HA and HA/CHX showed that both biomaterials did not present significant in vitro toxicity. Moreover, HA/CHX inhibited Enterococcus faecalis growth for up to 6 days, revealing that binding to HA did not affect antimicrobial activity of CHX and reduced bacterial adhesion. These results suggested that HA/CHX association could result in a potential adjuvant antimicrobial system for clinical use.
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2.82Impact points
Understanding the impact of divalent cation substitution on hydroxyapatite: an in vitro multiparametric study on biocompatibility.
Journal of biomedical materials research. Part A. 05/2011; 98(3):351-8.
Hydroxyapatite (HA), a stable and biocompatible material for bone tissue therapy, may present a variable stoichiometry and accept a large number of cationic substitutions. Such substitutions may modify the chemical activity of HA surface, with possible impact on biocompatibility. In this work, we as... [more] Hydroxyapatite (HA), a stable and biocompatible material for bone tissue therapy, may present a variable stoichiometry and accept a large number of cationic substitutions. Such substitutions may modify the chemical activity of HA surface, with possible impact on biocompatibility. In this work, we assessed the effects of calcium substitution with diverse divalent cations (Pb(2+), Sr(2+), Co(2+), Zn(2+), Fe(2+), Cu(2+), or Mg(2+)) on the biological behavior of HA. Physicochemical analyses revealed that apatite characteristics related to crystallinity and calcium dissolution/uptake rates are very sensitive to the nature of cationic substitution. Cytocompatibility was evaluated by mitochondrial activity, membrane integrity, cell density, proapoptotic potential, and adhesion tests. With the exception of Zn-HA, all the substituted HAs induced some level of apoptosis. The highest apoptosis levels were observed for Mg-HA and Co-HA. Cu-HA was the only material to impair simultaneously mitochondrial activity, membrane integrity, and cell density. The highest relative cell densities after exposure to the modified HAs were observed for Mg-HA and Zn-HA, while Co-HA significantly improved cell adhesion onto HA surface. These results show that changes on surface dissolution caused by cationic substitution, as well as the increase of metal species released to biological media, were the main responsible factors related to alterations on HA biocompatibility.
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1.51Impact points
The effect of alterations on resorbable blasting media processed implant surfaces on early bone healing: a study in rabbits.
Implant dentistry. 04/2011; 20(2):167-77.
Etching resorbable blasting media (RM) processed implants is a common engineering procedure, but the interplay between the resulting physicochemical properties and its effects on early bone healing have not been thoroughly addressed. Screw-root form implant surfaces were treated with 1 of 3 methods:... [more] Etching resorbable blasting media (RM) processed implants is a common engineering procedure, but the interplay between the resulting physicochemical properties and its effects on early bone healing have not been thoroughly addressed. Screw-root form implant surfaces were treated with 1 of 3 methods: grit (alumina) blasted/acid etching, RM, and RM + acid etching (RMAA). Surface topography (n = 3 each) was characterized by scanning electron microscopy and atomic force microscopy and chemical characterization by x-ray photoelectron spectroscopy analysis. The implants were placed at the distal femur of 16 rabbits, where 3 implants, 1 from each surface, were placed bilaterally remaining 4 and 8 weeks in vivo. After euthanization, one half of the specimens were torqued to interface failure at a rate of ∼0.196 radians/min and the other half were nondecalcified processed for histomorphology and bone-to-implant contact evaluation. Physicochemical characterization showed that the grit (alumina) blasted/acid-etched surface was rougher than RM and RMAA. Higher levels of calcium and phosphorous were observed for the RM surface compared with the RMAA surface. No significant differences were observed in torque and bone-to-implant contact between surfaces at 4 or 8 weeks. Histomorphologic evaluation showed woven bone formation around all surfaces at 4 weeks, and its initial replacement by lamellar bone at 8 weeks. Despite differences in texture/chemistry, all implant surfaces were biocompatible and osseoconductive, and led to comparable in vivo bone fixation and measurable histomorphometric parameters.
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2.82Impact points
Biological behavior of pre-osteoblasts on natural hydroxyapatite: a study of signaling molecules from attachment to differentiation.
Journal of biomedical materials research. Part A. 03/2011; 97(2):193-200.
Several biomaterials have been widely used in bone regeneration in both orthopedic and oral surgeries. However, it is poorly understood how these biomaterials alter osteoblast phenotype. It prompted us to examine the involvement of signaling proteins during preosteoblast adhesion (attachment), proli... [more] Several biomaterials have been widely used in bone regeneration in both orthopedic and oral surgeries. However, it is poorly understood how these biomaterials alter osteoblast phenotype. It prompted us to examine the involvement of signaling proteins during preosteoblast adhesion (attachment), proliferation, and differentiation on natural hydroxyapatite (HA) from bovine bone. Our results indicated that natural HA is able to promote osteoblast adhesion, proliferation, and differentiation. The osteoblast/HA interaction requires phosphorylation of tyrosine residues of focal adhesion kinase, Src, and Paxillin upon integrin activation, which culminates in the control of cofilin phosphorylation (at serine 03) via rac-1 activation. In part, these signaling pathways are responsible for actin-rearrangement, responsible to adapt cell-shape on HA particles. In regarding to osteoblast differentiation, we showed that natural HA favored extracellular matrix remodeling by stimulating matrix metalloproteinase activities and alkaline phosphatase activity. Overall, this study demonstrates that osteoblast response toward bovine bone HA is initially mediated by activation of focal adhesion components, culminating on actin-rearrangement executed by cofilin activation via rac-1. Moreover, bovine bone HA provided an excellent microenvironment for osteoblast activity, since adhesion to differentiation.
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1.96Impact points
Biological monitoring of a xenomaterial for grafting: an evaluation in critical-size calvarial defects.
Journal of materials science. Materials in medicine. 03/2011; 22(4):997-1004.
Our purpose was to evaluate the osteoconduction potential of mixed bovine bone (MBB) xenografts as an alternative for bone grafting of critical-size defects in the calvaria of rats. After surgery, in the time intervals of 1, 3, 6, and 9 months, rats were killed and their skulls collected, radiograph... [more] Our purpose was to evaluate the osteoconduction potential of mixed bovine bone (MBB) xenografts as an alternative for bone grafting of critical-size defects in the calvaria of rats. After surgery, in the time intervals of 1, 3, 6, and 9 months, rats were killed and their skulls collected, radiographed and histologically prepared for analysis. The data obtained from histological analysis reported that the particles of MBB did not promote an intense immunological response, evidencing its biocompatibility in rats. Our results clearly showed the interesting evidence that MBB was not completely reabsorbed at 9 months while a small amount of newly formed bone was deposited by osteoprogenitor cells bordering the defect. However, this discrete bone-forming stimulation was unable to regenerate the bone defect. Overall, our results suggest that the properties of MBB are not suitable for stimulating intense bone regeneration in critical bone defects in rats.
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2.92Impact points
Biological monitoring of a promissory xenogenic pin for biomedical applications: a preliminary intraosseous study in rats.
Clinical oral implants research. 03/2011; 23(3):367-372.
Objectives: Over the last years, it is known that in some cases metal devices for biomedical applications present some disadvantages suggesting absorbable materials (natural or synthetic) as an alternative of choice. Here, our goal was to evaluate the biological response of a xenogenic pin, derived ... [more] Objectives: Over the last years, it is known that in some cases metal devices for biomedical applications present some disadvantages suggesting absorbable materials (natural or synthetic) as an alternative of choice. Here, our goal was to evaluate the biological response of a xenogenic pin, derived from bovine cortical bone, intraosseously implanted in the femur of rats. Material and methods: After 10, 14, 30 and 60 days from implantation, the animals (n=5/period) were killed and the femurs carefully collected and dissected out under histological demands. For identifying the osteoclastogenesis level at 60 days, we performed the immunohistochemisty approach using antibody against RANKL. Results: Interestingly, our results showed that the incidence of neutrophils and leukocytes was observed only at the beginning (10 days). Clear evidences of pin degradation by host cells started at 14 days and it was more intensive at 60 days, when we detected the majority of the presence of giant multinucleated cells, which were very similar to osteoclast cells contacting the implanted pin. To check osteoclastogenesis at 60 days, we evaluated RANKL expression and it was positive for those resident multinucleated cells while a new bone deposition was verified surrounding the pins in all evaluated periods. Conclusions: Altogether, our results showed that pins from fully processed bovine bone are biocompatible and absorbable, allowing bone neoformation and it is a promissory device for biomedical applications. To cite this article: Zambuzzi WF, Oliveira RC, Subitoni BL, Menezes R, Taga R, Granjeiro, JM. Biological monitoring of a promissory xenogenic pin for biomedical applications: a preliminary intraosseous study in rats. Clin. Oral Impl. Res. 23, 2012; 367-372. doi: 10.1111/j.1600-0501.2010.02143.x.
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3.38Impact points
Intracellular signal transduction as a factor in the development of "smart" biomaterials for bone tissue engineering.
Biotechnology and bioengineering. 02/2011; 108(6):1246-50.
Signal transduction involves studying the intracellular mechanisms that govern cellular responses to external stimuli such as hormones, cytokines, and also cell adhesion to biomaterials surfaces. Several events have been shown to be responsible for cellular adhesion and adaptation onto different sur... [more] Signal transduction involves studying the intracellular mechanisms that govern cellular responses to external stimuli such as hormones, cytokines, and also cell adhesion to biomaterials surfaces. Several events have been shown to be responsible for cellular adhesion and adaptation onto different surfaces. For instance, cytoskeletal rearrangements during cell adhesion require the recruitment of specific protein tyrosine kinases into focal adhesion structures that promote transient focal adhesion kinase and Src phosphorylations, initially modulating cell behavior. In addition, the phosphorylation of tyrosine (Y) residues have been generally accepted as a critical regulator of a wide range of cell-related processes, including cell proliferation, migration, differentiation, survival signalling, and energy metabolism. The understanding of the signaling involved on the mechanisms of osteoblast adhesion, proliferation, and differentiation on implant surfaces is fundamental for the successful design of novel "smart" materials, potentially decreasing the repair time, thereby allowing for faster patient rehabilitation.
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Supernumerary teeth vary depending on gender.
Brazilian oral research. 02/2011; 25(1):76-9.
The presence of supernumerary teeth (ST) is a dental developmental anomaly of patterning and morphogenesis. Its variability of morphology, location and developmental timing can shed light on its etiology. In this work we report ST patterns. Orthopantomograms of 1,166 pediatric subjects were examined... [more] The presence of supernumerary teeth (ST) is a dental developmental anomaly of patterning and morphogenesis. Its variability of morphology, location and developmental timing can shed light on its etiology. In this work we report ST patterns. Orthopantomograms of 1,166 pediatric subjects were examined and the morphology, location and timing of the formation of ST were determined. The frequency of supernumerary teeth in the studied population was 2.3% (n = 27). Twenty-five subjects presented one ST. Maxilla midline was the most commonly affected region (nine cases). We noted high incidence of conical morphology in the midline region. Only teeth with tuberculate morphology presented delayed formation. ST in the midline region occurred more often in males whereas ST in the incisor region were more common in females. In conclusion, ST patterns vary depending on gender.
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0.88Impact points
Side of dental anomalies and taurodontism as potential clinical markers for cleft subphenotypes.
The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. 01/2011; 48(1):103-8.
Objective: The aim of this work was to investigate in more detail the dental clinical features that could serve to define subphenotypes of oral clefts. Design: Dental records of oral cleft subjects from a group of 164 cases were examined, and 157 were included in this study. In addition, 65 families... [more] Objective: The aim of this work was to investigate in more detail the dental clinical features that could serve to define subphenotypes of oral clefts. Design: Dental records of oral cleft subjects from a group of 164 cases were examined, and 157 were included in this study. In addition, 65 families with two or more siblings born with clefts and 30 control families were evaluated to determine whether dental phenotypes were sporadic. Type of oral cleft and dental phenotypes (tooth agenesis, supernumerary teeth, taurodontism, dental transposition, and microdontia) outside the cleft area were investigated. Association of dental anomalies with preferential subtypes of cleft (subphenotype) was assessed. Results: A total of 74 subjects presented at least one developmental dental anomaly. Tooth agenesis was the most common dental anomaly (28.6%), followed by taurodontism (15.2%). Supernumerary teeth were associated with cleft palate only (p = .05). The absence of maxillary left lateral incisors was significantly associated with unilateral right cleft lip (p = .02). Bilateral clefts were strongly associated with bilateral dental anomalies (p < 0.001). In the cleft lip and palate group, tooth agenesis was associated with dental transposition (p = .03) and with supernumerary teeth (p = .009). Subjects with oral clefts have a higher risk of tooth agenesis (odds ratio = 3.33; 95% confidence interval, 1.18 to 10.13) and taurodontism (odds ratio = 3.95; 95% confidence interval, 2.28 to 6.82). Tooth agenesis, microdontic upper lateral incisors, and supernumerary teeth were most commonly found in unaffected siblings and parents of children born with clefts in comparison with families with no family history of clefts (p = .01). Conclusion: The preferential associations between specific cleft types with dental phenotypes suggest dental anomalies can be used as clinical markers to define the subphenotype isolated cleft lip and palate.
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Repair of critical-size defects with autogenous periosteum-derived cells combined with bovine anorganic apatite/collagen: an experimental study in rat calvaria.
Brazilian dental journal. 01/2011; 22(4):322-8.
The aim of this study was to evaluate the bone repair using autogenous periosteum-derived cells (PDC) and bovine anorganic apatite and collagen (HA-COL). PDC from Wistar rats (n=10) were seeded on HA-COL discs and subjected to osteoinduction during 6 days. Critical-size defects in rat calvarias were... [more] The aim of this study was to evaluate the bone repair using autogenous periosteum-derived cells (PDC) and bovine anorganic apatite and collagen (HA-COL). PDC from Wistar rats (n=10) were seeded on HA-COL discs and subjected to osteoinduction during 6 days. Critical-size defects in rat calvarias were treated with blood clot (G1), autogenous bone (G2), HA-COL (G3) and HA-COL combined with PDC (G4) (n=40), and then analyzed 1 and 3 months after surgeries. Radiographic analysis exhibited no significant temporal change. G1 and G2 had discrete new marginal bone, but the radiopacity of graft materials in G2, G3 and G4 impaired the detection of osteogenesis. At 3 months, histopathological analysis showed the presence of ossification islets in G1, which was more evident in G2, homogeneous new bone around HA-COL in G3 and heterogeneous new bone around HA-COL in G4 in addition to moderate presence of foreign body cells in G3 and G4. Histomorphometric analysis showed no change in the volume density of xenograft (p>0.05) and bone volume density in G2 was twice greater than in G1 and G4 after 3 months (p<0.05), but similar to G3. The PDC did not increase bone formation in vivo, although the biomaterial alone showed biocompatibility and osteoconduction capacity.
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1.65Impact points
MMP1 and MMP20 contribute to tooth agenesis in humans.
Archives of oral biology. 12/2010; 56(5):506-11.
Variations in genes that are critical for tooth formation may contribute to the tooth agenesis. MMPs are potential candidate genes for dental alterations based on the roles they play during embryogenesis. The aim of this study was to investigate the possible association between MMP1, MMP3, and MMP20... [more] Variations in genes that are critical for tooth formation may contribute to the tooth agenesis. MMPs are potential candidate genes for dental alterations based on the roles they play during embryogenesis. The aim of this study was to investigate the possible association between MMP1, MMP3, and MMP20 and tooth agenesis. One hundred sixty-seven nuclear families from two different populations were analysed, 116 from Brazil and 51 from Turkey. Probands had at least one congenitally missing tooth. DNA samples were obtained from blood or saliva samples and genotyping was performed using TaqMan chemistry. In addition, Mmp20 was selected for quantitative real-time polymerase chain reaction analysis with SYBR Green I Dye in mouse tooth development. Associations between tooth agenesis and MMP1 (p=0.007), and MMP20 (p=0.03) were found in Brazilian families. In the total dataset, MMP20 continued to be associated with tooth agenesis (p=0.01). Mmp20 was not expressed during the initial stages of tooth development. Our findings provide evidence that MMP1 and MMP20 play a role in human tooth agenesis.
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2.27Impact points
Studies with Wnt genes and nonsyndromic cleft lip and palate.
Birth defects research. Part A, Clinical and molecular teratology. 10/2010; 88(11):995-1000.
Clefts of the lip and/or palate (cleft lip/palate) are notable for their complex etiology. The WNT pathway regulates multiple developmental processes including craniofacial development and may play a role in cleft lip/palate and other defects of craniofacial development such as tooth agenesis. Varia... [more] Clefts of the lip and/or palate (cleft lip/palate) are notable for their complex etiology. The WNT pathway regulates multiple developmental processes including craniofacial development and may play a role in cleft lip/palate and other defects of craniofacial development such as tooth agenesis. Variations in WNT genes have been recently associated with cleft lip/palate in humans. In addition, two WNT genes, Wnt3 and Wnt9B, are located in the clf1 cleft locus in mice. We investigated 13 SNPs located in Wnt3A, Wnt5A, Wnt8A, Wnt11, Wnt3, and Wnt9B genes for association with cleft lip/palate subphenotypes in 463 cleft cases and 303 unrelated controls. Genotyping of selected polymorphisms was carried out using Taqman assays. PLINK 1.06 software was used to test for differences in allele frequencies of each polymorphism between affected and unaffected individuals. Haplotype analysis was also performed. Individuals carrying variant alleles in WNT3 presented an increased risk for cleft lip/palate (p = 0.0003; OR, 1.61; 95% CI, 1.29-2.02) in the population studied. Our results continue to support a role for WNT genes in the pathogenesis of cleft lip/palate. Although much remains to be learned about the function of individual WNT genes during craniofacial development, additional studies should focus on the identification of potentially functional variants in these genes as contributors to human clefting. Birth Defects Research (Part A), 2010. © 2010 Wiley-Liss, Inc.
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1.58Impact points
Effect of surface modifications on early bone healing around plateau root form implants: an experimental study in rabbits.
Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons. 07/2010; 68(7):1631-8.
The objective of the present study was to evaluate the biomechanical fixation and bone-to-implant contact (BIC) of plateau root form implants of varied surfaces. Plateau root form implants, 3.5 mm in diameter, 8 mm in length, with 4 surfaces (n = 16 each)--machined, alumina-blasted/acid-etched, alum... [more] The objective of the present study was to evaluate the biomechanical fixation and bone-to-implant contact (BIC) of plateau root form implants of varied surfaces. Plateau root form implants, 3.5 mm in diameter, 8 mm in length, with 4 surfaces (n = 16 each)--machined, alumina-blasted/acid-etched, alumina-blasted/acid-etched plus nanothickness bioceramic coating, and plasma-sprayed calcium-phosphate--were used. They were bilaterally placed at the distal femur of 16 New Zealand rabbits and remained in place for 2 and 4 weeks in vivo. After euthanizing the rabbits, the implants were subjected to torque to interface fracture and were subsequently processed as nondecalcified approximately 30-microm-thickness slides for histomorphologic analysis and BIC determination. Statistical analysis was performed using analysis of variance at the 95% level of significance, considering implantation time and implant surface as independent variables and the torque-to-interface fracture and BIC as dependent variables. The torque-to-interface fracture was significantly affected by the implant surface (P < .001) but was not affected by the implantation time (P > .20). The implantation time and implant surface had significant effects on the BIC (P < .04 and P < .001, respectively). The greatest torque-to-interface fracture and BIC was observed for the plasma-sprayed calcium-phosphate. The implant surface significantly influenced early bone healing around plateau root form implants.
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2.40Impact points
Follow-up association studies of chromosome region 9q and nonsyndromic cleft lip/palate.
American journal of medical genetics. Part A. 07/2010; 152A(7):1701-10.
Cleft lip/palate comprises a large fraction of all human birth defects, and is notable for its significant lifelong morbidity and complex etiology. Several studies have shown that genetic factors appear to play a significant role in the etiology of cleft lip/palate. Human chromosomal region 9q21 has... [more] Cleft lip/palate comprises a large fraction of all human birth defects, and is notable for its significant lifelong morbidity and complex etiology. Several studies have shown that genetic factors appear to play a significant role in the etiology of cleft lip/palate. Human chromosomal region 9q21 has been suggested in previous reports to contain putative cleft loci. Moreover, a specific region (9q22.3-34.1) was suggested to present a approximately 45% probability of harboring a cleft susceptibility gene. Fine mapping of 50 SNPs across the 9q22.3-34.11 region was performed to test for association with cleft lip/palate in families from United States, Spain, Turkey, Guatemala, and China. We performed family-based analyses and found evidence of association of cleft lip/palate with STOM (rs306796) in Guatemalan families (P = 0.004) and in all multiplex families pooled together (P = 0.002). This same SNP also showed borderline association in the US families (P = 0.04). Under a nominal value of 0.05, other SNPs also showed association with cleft lip/palate and cleft subgroups. SNPs in STOM and PTCH genes and nearby FOXE1 were further associated with cleft phenotypes in Guatemalan and Chinese families. Gene prioritization analysis revealed PTCH and STOM ranking among the top fourteen candidates for cleft lip/palate among 339 genes present in the region. Our results support the hypothesis that the 9q22.32-34.1 region harbors cleft susceptibility genes. Additional studies with other populations should focus on these loci to further investigate the participation of these genes in human clefting.
Following (13)
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Tania Mary Cestari
Universidade de São Paulo -
Clóvis Monteiro Bramante
Universidade de São Paulo -
Monica Maia
Universidade Federal Fluminense (UFF) -
Vanessa Soares Lara
Bauru School of Dentistry - University of São Paulo -
Ricardo Lasmar
Universidade Federal Fluminense (UFF)
