| First Author | Choi H | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 26046 | PubMed ID | 27180803 |
| Mgi Jnum | J:252548 | Mgi Id | MGI:6102655 |
| Doi | 10.1038/srep26046 | Citation | Choi H, et al. (2016) TGF-beta Signaling Regulates Cementum Formation through Osterix Expression. Sci Rep 6:26046 |
| abstractText | TGF-beta/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-beta signaling in mouse tooth development, we analyzed osteocalcin-Cre mediated Tgfbr2 (OC(Cre)Tgfbr2(fl/fl)) conditional knockout mice, which lacks functional TGF-beta receptor II (TbetaRII) 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-beta signaling through TbetaRII in cementogenesis, we established a mouse cementoblast model with decreased TbetaRII 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 TbetaRII. 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-beta signaling directly regulates Osx expression through a Smad-dependent pathway. These findings strongly suggest that TGF-beta signaling plays a major role as one of the upstream regulators of Osx in cementoblast differentiation and cementum formation. |
