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

Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells.
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Runx2/miR-3960/miR-2861正反馈环负责血管平滑肌细胞的成骨转分化

DOI:
10.1155/2015/624037
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发表时间:
2015
影响因子:
--
通讯作者:
Xie H
Xie H
中科院分区:
生物学3区
文献类型:
--
作者:
Xia ZY;Hu Y;Xie PL;Tang SY;Luo XH;Liao EY;Chen F;Xie H

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我们以前报道过Runx 2/miR-3960/miR-2861调节反馈环刺激成骨细胞分化。然而,这种反馈回路对血管平滑肌细胞(VSMCs)成骨转分化的影响仍不清楚。我们最近的研究表明,miR-2861和miR-3960的表达在β-甘油磷酸诱导的VSMC成骨转分化过程中显著增加。VSMC中miR-2861或miR-3960的过表达增强β-甘油磷酸盐诱导的成骨细胞生成,而miR-2861或miR-3960表达的抑制则减弱了它。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VSMC的成骨转分化,导致Runx 2蛋白产生增加。此外,Runx 2的过表达诱导VSMC中miR-2861和miR-3960的转录,并且Runx 2的敲低减弱β-甘油磷酸诱导的miR-2861和miR-3960的转录。因此,我们的数据表明Runx 2/miR-3960/miR-2861正反馈环在VSMC的成骨转分化中起重要作用,并有助于血管钙化。
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.
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