title: Vaspin regulates the osteogenic differentiation of MC3T3-E1 through the PI3K-Akt/miR-34c loop.
abstract: Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a newly discovered adipokine that widely participates in diabetes mellitus, polycystic ovarian syndrome and other disorders of metabolism. However, the effect of vaspin on the regulation of osteogenesis and the mechanism responsible are still unclear. Here, we found that vaspin can attenuate the osteogenic differentiation of the preosteoblast cell line MC3T3-E1 in a dose-dependent way; also, during this process, the expression of miRNA-34c (miR-34c) was significantly increased. Down-regulation of the expression of miR-34c in MC3T3-E1 diminished the osteogenic inhibitory effect of vaspin, while the up-regulation of miR-34c increased this effect through its target gene Runx2. Meanwhile, we found that vaspin could also activate the PI3K-Akt signalling pathway. Blocking the PI3K-Akt signalling pathway with specific inhibitors could decrease the osteogenic inhibitory effect of vaspin as well as the expression level of miR-34c. Furthermore, knock-down of miR-34c could promote the activation of Akt, which was probably realised by targeting c-met expression. Thus, PI3K-Akt and miR-34c constituted a modulation loop and controlled the expression of each other. Taken together, our study showed that vaspin could inhibit the osteogenic differentiation in vitro, and the PI3K-Akt/miR-34c loop might be the underlying mechanism.
authors.affiliation: Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China.|Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Neurology, Xiangtan Central Hospital, Xiangtan, Hunan, People's Republic of China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Pei
authors.affiliation: Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China.|Department of Endocrinology, The Third Affilliated Hospital of Southern Medical University, Guangdong, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Endocrinology, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Cheng-Yuan
authors.initials: CY
authors.lastname: Song
authors.affiliation: Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Qiu-Hua
authors.initials: QH
authors.lastname: Liang
authors.affiliation: Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
authors.affiliation: Institute of Metabolism and Endocrinology, Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Ling-Qing
authors.initials: LQ
authors.lastname: Yuan
mesh_terms: D054392:Adipokines / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009025:Morpholines / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015843:Serpins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D054392:Adipokines; D000469:Alkaline Phosphatase; D002867:Chromones; D050659:Core Binding Factor Alpha 1 Subunit; D048049:Extracellular Signal-Regulated MAP Kinases; D035683:MicroRNAs; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019859:Proto-Oncogene Proteins c-met; D015843:Serpins; C551848:MIRN34a microRNA, mouse; C577327:vaspin protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one