title: Involvement of the phosphoinositide 3-kinase/Akt signaling pathway in bone morphogenetic protein 9-stimulated osteogenic differentiation and stromal cell-derived factor 1 production in human periodontal ligament fibroblasts.
abstract: Recent studies have shown that bone morphogenetic protein 9 (BMP-9) can induce osteogenic differentiation in human periodontal stem cells and human periodontal ligament fibroblasts (PDLFs). Bone morphogenetic protein 9 may be used in periodontal tissue regeneration because of its potent osteoinductive ability. Human periodontal ligament cells also have been demonstrated to produce stromal cell-derived factor 1 (SDF-1), which is important for stem-cell homing and recruitment to injured sites. In the present study, we examined the involvement of the phosphoinositide 3-kinase (PI3K)/Akt signaling axis in osteogenic differentiation and SDF-1 production in human PDLFs stimulated with BMP-9 in osteogenic medium supplemented with dexamethasone and ascorbic acid. Pretreatment of the cells with LY294002, a PI3K-specific inhibitor, suppressed not only BMP-9-enhanced alkaline phosphatase activity but also expression of a BMP-response gene (inhibitor of DNA binding 1) and osteogenic marker genes (runt-related transcription factor 2, osterix, bone sialoprotein, and osteopontin). In addition, BMP-9 up-regulated SDF-1 production, and the production of SDF-1 was suppressed by LY294002. The protein SDF-1-alpha was identified as a major isoform of SDF-1 that was regulated by BMP-9. Our data suggest involvement of the PI3K/Akt pathway in BMP-9-stimulated osteogenic differentiation and SDF-1 production in PDLFs cultured in osteogenic medium.
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kirara
authors.initials: K
authors.lastname: Furue
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kotaro
authors.identifier: 0000-0003-0612-1826
authors.initials: K
authors.lastname: Sena
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakoda
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Periodontology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Noguchi
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D055427:Growth Differentiation Factor 2 / Q000494:pharmacology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D010012:Osteogenesis / Q000502:physiology*; D010513:Periodontal Ligament / Q000166:cytology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D054377:Chemokine CXCL12; D002867:Chromones; D055427:Growth Differentiation Factor 2; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000469:Alkaline Phosphatase
keywords: bone morphogenetic protein 9; osteogenesis; periodontal ligament fibroblasts; phosphoinositide 3-kinase; stromal cell-derived factor 1