title: Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells.
abstract: We previously reported that Runx2/miR-3960/miR-2861 regulatory feedback loop stimulates osteoblast differentiation. However, the effect of this feedback loop on the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) remains unclear. Our recent study showed that miR-2861 and miR-3960 expression increases significantly during β-glycerophosphate-induced osteogenic transdifferentiation of VSMCs. Overexpression of miR-2861 or miR-3960 in VSMCs enhances β-glycerophosphate-induced osteoblastogenesis, whereas inhibition of miR-2861 or miR-3960 expression attenuates it. MiR-2861 or miR-3960 promotes osteogenic transdifferentiation of VSMCs by targeting histone deacetylase 5 or Homeobox A2, respectively, resulting in increased runt-related transcription factor 2 (Runx2) protein production. Furthermore, overexpression of Runx2 induces miR-2861 and miR-3960 transcription, and knockdown of Runx2 attenuates β-glycerophosphate-induced miR-2861 and miR-3960 transcription in VSMCs. Thus, our data show that Runx2/miR-3960/miR-2861 positive feedback loop plays an important role in osteogenic transdifferentiation of VSMCs and contributes to vascular calcification.
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Zhu-Ying
authors.initials: ZY
authors.lastname: Xia
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science of Central South University, Changsha, Hunan 410013, China.
authors.forename: Ping-Li
authors.initials: PL
authors.lastname: Xie
authors.affiliation: School of Nursing of Central South University, Changsha, Hunan 410013, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Tang
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Xiang-Hang
authors.initials: XH
authors.lastname: Luo
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Er-Yuan
authors.initials: EY
authors.lastname: Liao
authors.affiliation: Spine Surgery Department, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.affiliation: Institute of Endocrinology and Metabolism, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
mesh_terms: D000818:Animals; D054338:Cell Transdifferentiation / Q000187:drug effects / Q000235:genetics*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D005994:Glycerophosphates; D018398:Homeodomain Proteins; C489833:Hoxa2 protein, mouse; C000607173:MIRN2861 microRNA, mouse; C000607172:MIRN3960 microRNA, mouse; D035683:MicroRNAs; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases; C031463:beta-glycerophosphoric acid