Vinicio de Jesus Perez MD

Publication Details

  • MiR-133a modulates osteogenic differentiation of vascular smooth muscle cells. Endocrinology Liao, X. B., Zhang, Z. Y., Yuan, K., Liu, Y., Feng, X., Cui, R. R., Hu, Y. R., Yuan, Z. S., Gu, L., Li, S. J., Mao, D. A., Lu, Q., Zhou, X. M., de Jesus Perez, V. A., Yuan, L. Q. 2013

    Abstract:

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

    View details for PubMedID 23798596

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