title: Apelin stimulates proliferation and suppresses apoptosis of mouse osteoblastic cell line MC3T3-E1 via JNK and PI3-K/Akt signaling pathways.
abstract: The aim of this study was to investigate the effects of apelin on proliferation and apoptosis of mouse osteoblastic MC3T3-E1 cells. APJ was expressed in MC3T3-E1 cells. Apelin did not affect Runx2 expression, alkaline phosphatase (ALP) activity, osteocalcin and type I collagen secretion, suggesting that it has no effect on osteoblastic differentiation of MC3T3-E1 cells. However, apelin stimulated MC3T3-E1 cell proliferation and inhibited cell apoptosis induced by serum deprivation. Our study also shows that apelin decreased cytochrome c release and caspase-3, capase-8 and caspase-9 activation in serum-deprived MC3T3-E1 cells. Apelin activated c-Jun N-terminal kinase (JNK) and Akt (phosphatidylinositol 3-kinase downstream effector), and the JNK inhibitor SP600125, the phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 or the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO) inhibited its effects on proliferation and serum deprivation-induced apoptosis. Furthermore, apelin protected against apoptosis induced by the glucocorticoid dexamethasone or TNF-alpha. Apelin stimulates proliferation and suppresses serum deprivation-induced apoptosis of MC3T3-E1 cells and these actions are mediated via JNK and PI3-K/Akt signaling pathways.
authors.affiliation: The School of Nursing of Central South University, 172# Tongzipo Road, Changsha, Hunan 410013, PR China. tangsyuan@yahoo.com.cn
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Tang
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Ling-Qing
authors.initials: LQ
authors.lastname: Yuan
authors.forename: Xiang-Hang
authors.initials: XH
authors.lastname: Luo
authors.forename: Jiao
authors.initials: J
authors.lastname: Huang
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Cui
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhou
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Wu
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
mesh_terms: D016475:3T3 Cells; D054392:Adipokines; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D002352:Carrier Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C493716:Runx2 protein, mouse; D045304:Cytochromes c; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases