title: Ameloblastin regulates osteogenic differentiation by inhibiting Src kinase via cross talk between integrin beta1 and CD63.
abstract: Ameloblastin, the most abundant nonamelogenin enamel matrix protein, plays a role in ameloblast differentiation. Here, we found that ameloblastin was expressed in osteosarcoma cells; to explore the potential functions of ameloblastin in osteoblasts, we investigated whether this protein is involved in osteogenic differentiation and bone formation on the premise that CD63, a member of the transmembrane-4 glycoprotein superfamily, interacts with integrins in the presence of ameloblastin. Ameloblastin bound to CD63 and promoted CD63 binding to integrin β1. The interaction between CD63 and integrin β1 induced Src kinase inactivation via the binding of CD63 to Src. The reduction of Src activity and osteogenic differentiation mediated by ameloblastin were abrogated by treatment with anti-CD63 antibody and overexpression of constitutively active Src, respectively. Therefore, our results suggest that ameloblastin is expressed in osteoblasts and functions as a promoting factor for osteogenic differentiation via a novel pathway through the interaction between CD63 and integrin β1.
authors.affiliation: Department of Oral and Maxillofacial Pathobiology, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Iizuka
authors.forename: Yasusei
authors.initials: Y
authors.lastname: Kudo
authors.forename: Maki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tsunematsu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yoshiko
authors.forename: Takashi
authors.initials: T
authors.lastname: Uchida
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogawa
authors.forename: Mutsumi
authors.initials: M
authors.lastname: Miyauchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D003746:Dental Enamel Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D008903:Minerals / Q000378:metabolism; D008954:Models, Biological; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D060149:Tetraspanin 30; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C490889:AMBN protein, human; C098519:Ambn protein, rat; D015703:Antigens, CD; C554586:CD63 protein, human; C554588:Cd63 protein, rat; D017931:DNA Primers; D003746:Dental Enamel Proteins; D019012:Integrin beta1; D008903:Minerals; D010980:Platelet Membrane Glycoproteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D060149:Tetraspanin 30; D019061:src-Family Kinases