Xia Zhu-Ying, Hu Yin, Xie Ping-Li, Tang Si-Yuan, Luo Xiang-Hang, Liao Er-Yuan, Chen Fei, Xie Hui
Institute of Endocrinology and Metabolism, Second Xiang-Ya Hospital of Central South University, Changsha, Hunan 410011, China.
Department of Forensic Medicine, School of Basic Medical Science of Central South University, Changsha, Hunan 410013, China.
Biomed Res Int. 2015;2015:624037. doi: 10.1155/2015/624037. Epub 2015 Jun 28.
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.
我们之前报道过，Runx2/miR - 3960/miR - 2861调控反馈环可刺激成骨细胞分化。然而，该反馈环对血管平滑肌细胞（VSMCs）成骨转分化的影响仍不清楚。我们最近的研究表明，在β - 甘油磷酸诱导的VSMCs成骨转分化过程中，miR - 2861和miR - 3960的表达显著增加。在VSMCs中过表达miR - 2861或miR - 3960可增强β - 甘油磷酸诱导的成骨细胞生成，而抑制miR - 2861或miR - 3960的表达则会减弱这种作用。miR - 2861或miR - 3960分别通过靶向组蛋白去乙酰化酶5或同源框A2促进VSMCs的成骨转分化，导致与矮小相关转录因子2（Runx2）蛋白产量增加。此外，Runx2的过表达诱导miR - 2861和miR - 3960的转录，而敲低Runx2则会减弱β - 甘油磷酸诱导的VSMCs中miR - 2861和miR - 3960的转录。因此，我们的数据表明，Runx2/miR - 3960/miR - 2861正反馈环在VSMCs的成骨转分化中起重要作用，并促进血管钙化。
