title: Scleraxis and osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone.
abstract: The periodontal ligament (PDL) is a mechanosensitive noncalcified fibrous tissue connecting the cementum of the tooth and the alveolar bone. Here, we report that scleraxis (Scx) and osterix (Osx) antagonistically regulate tensile force-responsive PDL fibrogenesis and osteogenesis. In the developing PDL, Scx was induced during tooth eruption and co-expressed with Osx. Scx was highly expressed in elongated fibroblastic cells aligned along collagen fibers, whereas Osx was highly expressed in the perialveolar/apical osteogenic cells. In an experimental model of tooth movement, Scx and Osx expression was significantly upregulated in parallel with the activation of bone morphogenetic protein (BMP) signaling on the tension side, in which bone formation compensates for the widened PDL space away from the bone under tensile force by tooth movement. Scx was strongly expressed in Scx(+)/Osx(+) and Scx(+)/Osx(-) fibroblastic cells of the PDL that does not calcify; however, Scx(-)/Osx(+) osteogenic cells were dominant in the perialveolar osteogenic region. Upon BMP6-driven osteoinduction, osteocalcin, a marker for bone formation was downregulated and upregulated by Scx overexpression and knockdown of endogenous Scx in PDL cells, respectively. In addition, mineralization by osteoinduction was significantly inhibited by Scx overexpression in PDL cells without affecting Osx upregulation, suggesting that Scx counteracts the osteogenic activity regulated by Osx in the PDL. Thus, Scx(+)/Osx(-), Scx(+)/Osx(+) and Scx(-)/Osx(+) cell populations participate in the regulation of tensile force-induced remodeling of periodontal tissues in a position-specific manner.
authors: Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors: Aki
authors: A
authors: Takimoto
authors: Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan Department of Orthodontic and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
authors: Masayoshi
authors: M
authors: Kawatsu
authors: Department of Molecular Biology and Biochemistry, Division of Basic Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
authors: Yuki
authors: Y
authors: Yoshimoto
authors: Radioisotope Research Institute, Tsurumi University School of Dental Medicine, Tsurumi, Yokohama 230-8501, Japan.
authors: Tadafumi
authors: T
authors: Kawamoto
authors: Department of Orthodontic and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
authors: Masahiro
authors: M
authors: Seiryu
authors: Department of Orthodontic and Dentofacial Orthopedics, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan.
authors: Teruko
authors: T
authors: Takano-Yamamoto
authors: Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors: Yuji
authors: Y
authors: Hiraki
authors: Department of Cellular Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan Department of Molecular Biology and Biochemistry, Division of Basic Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan shukunam@hiroshima-u.ac.jp.
authors: Chisa
authors: C
authors: Shukunami
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010513:Periodontal Ligament / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar; D000076182:Sp7 Transcription Factor; D013718:Tensile Strength / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors; C503815:Scx protein, mouse; C479466:Sp7 protein, mouse
keywords: Mouse; Osterix; Periodontal ligament; Scleraxis; Tensile force