title: Bone morphogenetic protein 7 induces cementogenic differentiation of human periodontal ligament-derived mesenchymal stem cells.
abstract: Bone morphogenetic protein 7 (BMP-7) is a multifunctional differentiation factor that belongs to the transforming growth factor superfamily. BMP-7 induces gene expression of protein tyrosine phosphatase-like, member A/cementum attachment protein (PTPLA/CAP) and cementum protein 1 (CEMP1), both of which are markers of cementoblasts and cementocytes. In the previous study, we reported that BMP-7 treatment enhanced PTPLA/CAP and CEMP1 expression in both normal and immortal human periodontal ligament (PDL) cells. To elucidate the molecular mechanisms of the gene expression of these molecules, in this study, we identified a functional transcription activator binding region in the promoter region of PTPLA/CAP and CEMP1 that is responsive to BMP signals. Here, we report that some short motifs termed GC-rich Smad-binding elements (GC-SBEs) that are located in the human PTPLA/CAP promoter and CEMP1 promoter are BMP-7 responsive as analyzed with luciferase promoter assays. On the other hand, we found that transcription of Sp7/Osterix and PTPLA/CAP was up-regulated after 1 week of BMP-7 treatment on purified normal human PDL cells as a result of gene expression microarray analysis. Furthermore, transcription of Sp7/Osterix, runt-related transcription factor 2 (RUNX2), and alkaline phosphatase (ALP) was up-regulated after 2 weeks of BMP-7 treatment, whereas gene expression of osteo/odontogenic markers such as integrin-binding sialoprotein (IBSP), collagen, type I, alpha 1 (COL1A1), dentin matrix acidic phosphoprotein 1 (DMP1), and dentin sialophosphoprotein (DSPP) was not up-regulated in purified normal or immortal human PDL cells as a result of qRT-PCR. The results suggest that BMP-7 mediates cementogenesis via GC-SBEs in human PDL cells and that its molecular mechanism is different from that for osteo/odontogenesis.
authors.affiliation: Department of Pharmacology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Torii
authors.affiliation: Department of Pharmacology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan.
authors.forename: T W
authors.initials: TW
authors.lastname: Tsutsui
authors.affiliation: Department of Human Genetics, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Microbiology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan. konikiyo@tky.ndu.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Konishi
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D003739:Dental Cementum / Q000166:cytology*; D003746:Dental Enamel Proteins / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology*; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism; D000099311:Dentin Sialophosphoprotein
chemical_list: D000469:Alkaline Phosphatase; D055419:Bone Morphogenetic Protein 7; D050659:Core Binding Factor Alpha 1 Subunit; D003746:Dental Enamel Proteins; D016326:Extracellular Matrix Proteins; D058574:Integrin-Binding Sialoprotein; D010750:Phosphoproteins; D011506:Proteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C510886:CEMP1 protein, human
keywords: Bone morphogenetic protein 7; Cementoblasts; Periodontal ligament