MiR-133a Modulates Osteogenic Differentiation of Vascular Smooth Muscle Cells

• DOI: 10.1210/en.2012-2236
• Publication Date: 2013-06-25T03:57:42Z
• Authors: Xiao-Bo Liao; Zhi-Yuan Zhang; Ke Yuan; Yuan Liu; Xiang Feng; Rong-Rong Cui; Ye-Rong Hu; Zhao-Shun Yuan; Lu Gu; Shi-Jun Li; Ding-An Mao; Qiong Lu; Xin-Ming Zhou; Vinicio A. de Jes...; Ling-Qing Yuan
• Keywords: RUNX2; Transdifferentiation

Arterial calcification is a key pathologic component of vascular diseases such as atherosclerosis, coronary artery disease, and peripheral disease. A hallmark this pathological process the phenotypic transition smooth muscle cells (VSMCs) to osteoblast-like cells. Several studies have demonstrated that microRNAs (miRNAs) regulate osteoblast differentiation, but it unclear whether miRNAs also VSMC-mediated arterial calcification. In present study, we sought characterize role miR-133a in regulating Northern blotting analysis VSMCs treated with β-glycerophosphate was significantly decreased during osteogenic differentiation. Overexpression inhibited VSMC transdifferentiation into evidenced by decrease alkaline phosphatase activity, osteocalcin secretion, Runx2 expression, mineralized nodule formation. Conversely, knockdown using an inhibitor promoted differentiation increasing expression. identified direct target cotransfection experiment luciferase reporter plasmids containing wild-type or mutant 3'-untranslated region sequences Runx2. Furthermore, pro-osteogenic effects were abrogated Runx2-knockdown cells, inhibition pre-miR-133a reversed overexpression Runx2, providing functional evidence mediated targeting These results demonstrate negative regulator VSMCs.