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BioMed Research International
Volume 2015, Article ID 624037, 7 pages
http://dx.doi.org/10.1155/2015/624037
Research Article

Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells

1Institute of Endocrinology and Metabolism, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China
2Department of Forensic Medicine, School of Basic Medical Science of Central South University, Changsha, Hunan 410013, China
3School of Nursing of Central South University, Changsha, Hunan 410013, China
4Spine Surgery Department, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China

Received 15 August 2014; Accepted 2 January 2015

Academic Editor: Xiao-Bo Liao

Copyright © 2015 Zhu-Ying Xia et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.