title: TGF-β Signaling Regulates Cementum Formation through Osterix Expression.
abstract: 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 cementum mass with reduced matrix secretion and mineral apposition rates. To explore the molecular mechanisms underlying the roles of TGF-β signaling through TβRII in cementogenesis, we established a mouse cementoblast model with decreased TβRII 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 TβRII. 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-β signaling directly regulates Osx expression through a Smad-dependent pathway. These findings strongly suggest that TGF-β signaling plays a major role as one of the upstream regulators of Osx in cementoblast differentiation and cementum formation.
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 54896, South Korea.
authors.forename: Hwajung
authors.initials: H
authors.lastname: Choi
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 54896, South Korea.
authors.forename: Yu-Hyun
authors.initials: YH
authors.lastname: Ahn
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 54896, South Korea.
authors.forename: Tak-Heun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 54896, South Korea.
authors.forename: Cheol-Hyeon
authors.initials: CH
authors.lastname: Bae
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 54896, South Korea.
authors.forename: Jeong-Chae
authors.initials: JC
authors.lastname: Lee
authors.affiliation: Department of Periodontology, School of Dentistry, Wonkwang University, Iksan 54538, South Korea.
authors.forename: Hyung-Keun
authors.initials: HK
authors.lastname: You
authors.affiliation: Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences, Chonbuk National University School of Dentistry, Jeonju 54896, South Korea.
authors.forename: Eui-Sic
authors.initials: ES
authors.lastname: Cho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D025021:Cementogenesis / Q000235:genetics*; D003739:Dental Cementum / Q000502:physiology*; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015675:Osteocalcin / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D000076182:Sp7 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C480020:Atrnl1 protein, mouse; D008565:Membrane Proteins; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D000076182:Sp7 Transcription Factor; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II