Oncostatin M Promotes Osteoblastic Differentiation of Human Vascular Smooth Muscle Cells Through JAK3-STAT3 Pathway
Abstract
Vascular calcification is a clinically significant component of atherosclerosis and arises from chronic vascular inflammation. Oncostatin M (OSM) derived from plaque macrophages may contribute to the development of atherosclerotic calcification. Here, we investigated the stimulatory effects of OSM on osteoblastic differentiation of human vascular smooth muscle cells (HVSMC) derived from various arteries including umbilical artery, aorta, and coronary artery and its signaling pathway. Osteoblastic differentiation was induced by exposure of HVSMC to osteogenic differentiation medium (ODM) (10% fetal bovine serum, 0.1 μM dexamethasone, 10 mM β-glycerophosphate and 50 μg/ml ascorbic acid 2-phosphate in Dulbecco's modified Eagle's medium [DMEM]). OSM significantly increased alkaline phosphate (ALP) activity and matrix mineralization in HVSMC from all sources. Osteoblast marker genes such as ALP and Runx2 were also up-regulated by OSM in these cells. OSM treatment induced activation of STAT3 in HVSMC from umbilical artery as evidenced by immunoblot. Moreover, not only a JAK3 inhibitor, WHI-P154, but also knockdown of JAK3 by siRNA prevented the OSM-induced ALP activity and matrix mineralization in umbilical artery HVSMC. On the other...Continue Reading
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