Dataset Information

TGF-? Signaling Regulates Cementum Formation through Osterix Expression.

ABSTRACT: TGF-?/BMPs have widely recognized roles in mammalian development, including in bone and tooth formation. To define the functional relevance of the autonomous requirement for TGF-? signaling in mouse tooth development, we analyzed osteocalcin-Cre mediated Tgfbr2 (OC(Cre)Tgfbr2(fl/fl)) conditional knockout mice, which lacks functional TGF-? receptor II (T?RII) in differentiating cementoblasts and cementocytes. Strikingly, OC(Cre)Tgfbr2(fl/fl) mutant mice exhibited a sharp reduction in cellular cementum mass with reduced matrix secretion and mineral apposition rates. To explore the molecular mechanisms underlying the roles of TGF-? signaling through T?RII in cementogenesis, we established a mouse cementoblast model with decreased T?RII expression using OCCM-30 cells. Interestingly, the expression of osterix (Osx), one of the major regulators of cellular cementum formation, was largely decreased in OCCM-30 cells lacking T?RII. Consequently, in those cells, functional ALP activity and the expression of genes associated with cementogenesis were reduced and the cells were partially rescued by Osx transduction. We also found that TGF-? signaling directly regulates Osx expression through a Smad-dependent pathway. These findings strongly suggest that TGF-? signaling plays a major role as one of the upstream regulators of Osx in cementoblast differentiation and cementum formation.

SUBMITTER: Choi H

PROVIDER: S-EPMC4867644 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

TGF-β Signaling Regulates Cementum Formation through Osterix Expression.

Choi Hwajung H Ahn Yu-Hyun YH Kim Tak-Heun TH Bae Cheol-Hyeon CH Lee Jeong-Chae JC You Hyung-Keun HK Cho Eui-Sic ES

Scientific reports 20160516

TGF-β/BMPs have widely recognized roles in mammalian development, including in bone and tooth formation. To define the functional relevance of the autonomous requirement for TGF-β signaling in mouse tooth development, we analyzed osteocalcin-Cre mediated Tgfbr2 (OC(Cre)Tgfbr2(fl/fl)) conditional knockout mice, which lacks functional TGF-β receptor II (TβRII) in differentiating cementoblasts and cementocytes. Strikingly, OC(Cre)Tgfbr2(fl/fl) mutant mice exhibited a sharp reduction in cellular cem ...[more]

PMID: 27180803

Similar Datasets

Project description:To investigate the role of IGF-I signaling in osterix (OSX)-expressing cells in the skeleton, we generated IGF-I receptor (IGF-IR) knockout mice ((OSX)IGF-IRKO) (floxed-IGF-IR mice × OSX promoter-driven GFP-labeled cre-recombinase [(OSX)GFPcre]), and monitored postnatal bone development. At day 2 after birth (P2), (OSX)GFP-cre was highly expressed in the osteoblasts in the bone surface of the metaphysis and in the prehypertrophic chondrocytes (PHCs) and inner layer of perichondral cells (IPCs). From P7, (OSX)GFP-cre was highly expressed in PHCs, IPCs, cartilage canals (CCs), and osteoblasts (OBs) in the epiphyseal secondary ossification center (SOC), but was only slightly expressed in the OBs in the metaphysis. Compared with the control mice, the IPC proliferation was decreased in the (OSX)IGF-IRKOs. In these mice, fewer IPCs invaded into the cartilage, resulting in delayed formation of the CC and SOC. Immunohistochemistry indicated a reduction of vessel number and lower expression of VEGF and ephrin B2 in the IPCs and SOC of (OSX)IGF-IRKOs. Quantitative real-time PCR revealed that the mRNA levels of the matrix degradation markers, MMP-9, 13 and 14, were decreased in the (OSX)IGF-IRKOs compared with the controls. The (OSX)IGF-IRKO also showed irregular morphology of the growth plate and less trabecular bone in the tibia and femur from P7 to 7 weeks, accompanied by decreased chondrocyte proliferation, altered chondrocyte differentiation, and decreased osteoblast differentiation. Our data indicate that during postnatal bone development, IGF-I signaling in OSX-expressing IPCs promotes IPC proliferation and cartilage matrix degradation and increases ephrin B2 production to stimulate vascular endothelial growth factor (VEGF) expression and vascularization. These processes are required for normal CC formation in the establishment of the SOC. Moreover, IGF-I signaling in the OSX-expressing PHC is required for growth plate maturation and osteoblast differentiation in the development of the metaphysis.

Dataset Information

TGF-? Signaling Regulates Cementum Formation through Osterix Expression.

Publications

TGF-β Signaling Regulates Cementum Formation through Osterix Expression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets