title: Adiponectin attenuates the osteoblastic differentiation of vascular smooth muscle cells through the AMPK/mTOR pathway.
abstract: Vascular calcification is common in patients with peripheral artery diseases and coronary artery diseases. The osteoblastic differentiation of vascular smooth muscle cells (VSMCs) contributes significantly to vascular calcification. Adiponectin has been demonstrated to exert a protective effect in osteoblastic differentiation of VSMCs through regulating mTOR activity. However, the upstream and downstream signaling molecules of adiponectin-regulated mTOR signaling have not been identified in VSMCs with osteoblastic differentiation. In this study, the VSMC differentiation model was established by beta-glycerophosphate (β-GP) induction. The mineralization was identified by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot or immunofluorescence. Adiponectin attenuated osteoblastic differentiation and mineralization of β-GP-treated VSMCs. Adiponectin inhibited osteoblastic differentiation of VSMCs through increasing the level of p-AMPKα. Pretreatment of VSMCs with AMPK inhibitor blocked while AMPK activator enhanced the effect of adiponectin on osteoblastic differentiation of VSMCs. Adiponectin upregulated TSC2 expression and downregulated mTOR and S6K1 phosphorylation in β-GP-treated VSMCs. Adiponectin treatment significantly attenuates the osteoblastic differentiation and calcification of VSMCs through modulation of AMPK-TSC2-mTOR-S6K1 signal pathway.
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-ya Hospital, Central South University, 139 Renmin Road, Changsha 410011, Hunan, PR China.
authors.forename: Jun-Kun
authors.initials: JK
authors.lastname: Zhan
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-ya Hospital, Central South University, 139 Renmin Road, Changsha 410011, Hunan, PR China.
authors.forename: Yan-Jiao
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-ya Hospital, Central South University, 139 Renmin Road, Changsha 410011, Hunan, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-ya Hospital, Central South University, 139 Renmin Road, Changsha 410011, Hunan, PR China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Tang
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-ya Hospital, Central South University, 139 Renmin Road, Changsha 410011, Hunan, PR China.
authors.forename: Pan
authors.initials: P
authors.lastname: Tan
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-ya Hospital, Central South University, 139 Renmin Road, Changsha 410011, Hunan, PR China.
authors.forename: Wu
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang-ya Hospital, Central South University, 139 Renmin Road, Changsha 410011, Hunan, PR China. Electronic address: Liuyoushuo@yeah.net.
authors.forename: You-Shuo
authors.initials: YS
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000494:pharmacology*; D002113:Calcification, Physiologic; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D005994:Glycerophosphates; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; D055372:AMP-Activated Protein Kinases; D002118:Calcium; C031463:beta-glycerophosphoric acid
keywords: AMPK/mTOR; Adiponectin; Osteoblastic differentiation; Vascular smooth muscle cells