title: Ghrelin attenuates the osteoblastic differentiation of vascular smooth muscle cells through the ERK pathway.
abstract: Vascular calcification results from osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and is a major risk factor for cardiovascular events. Ghrelin is a newly discovered bioactive peptide that acts as a natural endogenous ligand of the growth hormone secretagog receptor (GHSR). Several studies have identified the protective effects of ghrelin on the cardiovascular system, however research on the effects and mechanisms of ghrelin on vascular calcification is still quite rare. In this study, we determined the effect of ghrelin on osteoblastic differentiation of VSMCs and investigated the mechanism involved using the two universally accepted calcifying models of calcifying vascular smooth muscle cells (CVSMCs) and beta-glycerophosphate (beta-GP)-induced VSMCs. Our data demonstrated that ghrelin inhibits osteoblastic differentiation and mineralization of VSMCs due to decreased alkaline phosphatase (ALP) activity, Runx2 expression, bone morphogenetic protein-2 (BMP-2) expression and calcium content. Further study demonstrated that ghrelin exerted this suppression effect via an extracellular signal-related kinase (ERK)-dependent pathway and that the suppression effect of ghrelin was time dependent and dose dependent. Furthermore, inhibition of the growth hormone secretagog receptor (GHSR), the ghrelin receptor, by siRNA significantly reversed the activation of ERK by ghrelin. In conclusion, our study suggests that ghrelin may inhibit osteoblastic differentiation of VSMCs through the GHSR/ERK pathway.
authors.affiliation: Institute of Metabolism and Endocrinology, the Second Xiang-Ya Hospital, Central South University, Changsha, People's Republic of China.
authors.forename: Qiu-Hua
authors.initials: QH
authors.lastname: Liang
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Cui
authors.forename: Guan-Ying
authors.initials: GY
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Wu
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Liao
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.forename: Hou-De
authors.initials: HD
authors.lastname: Zhou
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Wu
authors.forename: Ling-Qing
authors.initials: LQ
authors.lastname: Yuan
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054439:Ghrelin / Q000494:pharmacology*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D054439:Ghrelin; D034741:RNA, Small Interfering; D054440:Receptors, Ghrelin; C493716:Runx2 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase