Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers ...Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers of the periodontal ligament （PDL）. However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 （Bmp2） in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 （PO）, followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2gene is removed from Sp7＋ （Osterix＋） cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC （Nfic）, periostin and α-SMA＋ cells. Third, there is a failure to produce vascular endothelial growth factor A （VEGF-A） in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOsp7-cre＇EGFe. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOsp7-cre＇EGFe. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.展开更多
Bone morphogenetic protein (BMP) can promote the proliferation of dental pulp cells and induce reparative dentin formation. In this study, the inductive effect of BMP derived from bovine bone matrix on cultured human ...Bone morphogenetic protein (BMP) can promote the proliferation of dental pulp cells and induce reparative dentin formation. In this study, the inductive effect of BMP derived from bovine bone matrix on cultured human dental pulp tissue was observed under light microscope and transmission electron microscope. The results showed that. by the third day of culture, the proliferating star-shaped cells appeared with small cytoplasm and poorly-developed organelles; by the 7th day of the culture, the chondroblast-like cells with rich cytoplasm and well-developed organelles were seen embedded in hyaline matrix. This study suggests that BMP can induce dental pulp cells to differentiate from poorly differentiated state to well-differentiated state.展开更多
Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is most...Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type Ⅰ procollagen.In this study,we identified a Thai patient having OI type Ⅲ,EDS,brachydactyly,and dentinogenesis imperfecta.His dentition showed delayed eruption,early exfoliation,and severe malocclusion.For the first time,ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion,bonelike dentin,loss of dentinal tubules,and reduction in hardness and elasticity,suggesting severe developmental disturbance.These severe dental defects have never been reported in OI or EDS.Exome sequencing identified a novel de novo heterozygous glycine substitution,c.3296G>A,p.Gly1099Glu,in exon 49 of COL1A2.Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage.Notably,two of these three patients did not show hyperextensible joints and hypermobile skin,while our patient at the age of 5 years had not developed intracranial hemorrhage.Here,we demonstrate that the novel glycine substitution in the carboxyl region of alpha2(Ⅰ)collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects,expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.展开更多
基金partly supported by research grant funding:NIH-NIAMS R01- AR054616 (SEH), NIH-NIDCR T32-DE14318 (Rakian) and F32-DE018865 (Yang)supported by UTHSCSA, NIH-NCI P30-CA54174 (CTRC at UTHSCSA) and NIH-NIA P01-AG19316supported by Open Fund of State Key Laboratory of Oral Diseases, Sichuan University
文摘Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers of the periodontal ligament （PDL）. However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 （Bmp2） in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 （PO）, followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2gene is removed from Sp7＋ （Osterix＋） cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC （Nfic）, periostin and α-SMA＋ cells. Third, there is a failure to produce vascular endothelial growth factor A （VEGF-A） in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOsp7-cre＇EGFe. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOsp7-cre＇EGFe. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.
文摘Bone morphogenetic protein (BMP) can promote the proliferation of dental pulp cells and induce reparative dentin formation. In this study, the inductive effect of BMP derived from bovine bone matrix on cultured human dental pulp tissue was observed under light microscope and transmission electron microscope. The results showed that. by the third day of culture, the proliferating star-shaped cells appeared with small cytoplasm and poorly-developed organelles; by the 7th day of the culture, the chondroblast-like cells with rich cytoplasm and well-developed organelles were seen embedded in hyaline matrix. This study suggests that BMP can induce dental pulp cells to differentiate from poorly differentiated state to well-differentiated state.
基金supported by the 90th Anniversary of Chulalongkorn University,Rachadapisek Sompote FundFaculty of Dentistry(DFR62003),Chulalongkorn University+3 种基金Chulalongkorn Academic Advancement Into Its 2nd Century ProjectNewton FundThailand Research Fund(RSA6280001,DPG6180001)supported by Ratchadapisek Somphot Fund for Postdoctoral Fellowship,Chulalongkorn University,Thailand。
文摘Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type Ⅰ procollagen.In this study,we identified a Thai patient having OI type Ⅲ,EDS,brachydactyly,and dentinogenesis imperfecta.His dentition showed delayed eruption,early exfoliation,and severe malocclusion.For the first time,ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion,bonelike dentin,loss of dentinal tubules,and reduction in hardness and elasticity,suggesting severe developmental disturbance.These severe dental defects have never been reported in OI or EDS.Exome sequencing identified a novel de novo heterozygous glycine substitution,c.3296G>A,p.Gly1099Glu,in exon 49 of COL1A2.Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage.Notably,two of these three patients did not show hyperextensible joints and hypermobile skin,while our patient at the age of 5 years had not developed intracranial hemorrhage.Here,we demonstrate that the novel glycine substitution in the carboxyl region of alpha2(Ⅰ)collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects,expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.
