title: Effect of Melatonin on the Extracellular-Regulated Kinase Signal Pathway Activation and Human Osteoblastic Cell Line hFOB 1.19 Proliferation.
abstract: It has been shown that melatonin may affect bone metabolism. However, it is controversial whether melatonin could promote osteoblast proliferation, and the precise molecular mechanism of melatonin on osteoblast proliferation is still obscure. In this study, the results of the CCK-8 assay showed that melatonin significantly promoted human osteoblastic cell line hFOB 1.19 cell proliferation at 1, 2.5, 5, 10, 25, 50 and 100 µM concentrations for 24 h, but there were no significant differences among the groups. Western blot demonstrated that 10 µM melatonin significantly promoted ERK1/2 phosphorylation. Furthermore, we also detected the phosphorylation of c-Raf, MEK1/2, p90RSK and MSK1, and all of them increased with 10 µM melatonin. U0126 (a selective inhibitor of MEK that disrupts downstream activation of ERK1/2) downregulated the phosphorylation of ERK1/2, p90RSK and MSK1. U0126 also attenuated the proliferation of osteoblasts stimulated by melatonin. In conclusion, this study for the first time indicates that melatonin (10 nM-100 µM) promotes the proliferation of a human osteoblastic cell line hFOB 1.19 through activation of c-Raf, MEK1/2, ERK1/2, p90RSK and MSK1.
authors.affiliation: Department of Orthopaedics, First Hospital, China Medical University, Shenyang 110001, China. doctxc@126.com.
authors.forename: Xiao-Chuan
authors.initials: XC
authors.lastname: Xiong
authors.affiliation: Department of Orthopaedics, First Hospital, China Medical University, Shenyang 110001, China. zhuyuedr@163.com.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedics, First Hospital, Dalian Medical University, Dalian 116011, China. cmu0204@126.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Ge
authors.affiliation: Department of Orthopaedics, East Hospital, Tongji University School of Medicine, Shanghai 200120, China. liulifengxy@163.com.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, First Hospital, China Medical University, Shenyang 110001, China. royvi218@sina.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
mesh_terms: D002460:Cell Line; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D008550:Melatonin