title: Distinction Between Cell Proliferation and Apoptosis Signals Regulated by Brain-Derived Neurotrophic Factor in Human Periodontal Ligament Cells and Gingival Epithelial Cells.
abstract: Previously, we reported that brain-derived neurotrophic factor (BDNF) enhances periodontal tissue regeneration by inducing periodontal ligament cell proliferation in vivo. In addition, the down growth of gingival epithelial cells, which comprises a major obstacle to the regeneration, was not observed. However, the underlying molecular mechanism is still unclear. Therefore, this study aimed to investigate the effect of BDNF on cell proliferation and apoptosis in human periodontal ligament (HPL) cells and human gingival epithelial cells (OBA9 cells) and to explore the molecular mechanism in vitro. HPL cells dominantly expressed a BDNF receptor, TrkB, and BDNF increased cell proliferation and ERK phosphorylation. However, its proliferative effect was diminished by a MEK1/2 inhibitor (U0126) and TrkB siRNA transfection. Otherwise, OBA9 cells showed a higher expression level of p75, which is a pan-neurotrophin receptor, than that of HPL cells. BDNF facilitated not cell proliferation but cell apoptosis and JNK phosphorylation in OBA9 cells. A JNK inhibitor (SP600125) and p75 siRNA transfection attenuated the BDNF-induced cell apoptosis. Moreover, OBA9 cells pretreated with SP600125 or p75 siRNA showed cell proliferation by BDNF stimulation, though it was reduced by U0126 and TrkB siRNA. Interestingly, overexpression of p75 in HPL cells upregulated cell apoptosis and JNK phosphorylation by BDNF treatment. These results indicated that TrkB-ERK signaling regulates BDNF-induced cell proliferation, whereas p75-JNK signaling plays roles in cell apoptotic and cytostatic effect of BDNF. Overall, BDNF activates periodontal ligament cells proliferation and inhibits the gingival epithelial cells growth via the distinct pathway. J. Cell. Biochem. 117: 1543-1555, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kashiwai
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ouhara
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Oral and Maxillofacial Pathology, Basic Life Sciences, Institute of Biomedical and Health Science, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
authors.affiliation: Center of Oral Clinical Examination, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Masae
authors.initials: M
authors.lastname: Kitagawa
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.affiliation: Department of Periodontal Medicine, Applied Life Sciences, Institute of Biomedical & Health Sciences, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005881:Gingiva / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human
keywords: BDNF; ERK; JNK; TrkB; p75