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...
Saved in:
Published in | Journal of cellular biochemistry Vol. 116; no. 7; pp. 1325 - 1333 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Blackwell Publishing Ltd
01.07.2015
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | 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 hand, silencing of STAT3 almost completely suppressed OSM‐induced ALP expression and matrix mineralization in HVSMC from all sources. These data suggest that OSM promotes osteoblastic differentiation of vascular smooth muscle cells through JAK3/STAT3 pathway and may contribute to the development of atherosclerotic calcification. J. Cell. Biochem. 116: 1325–1333, 2015. © 2015 Wiley Periodicals, Inc. |
---|---|
Bibliography: | ark:/67375/WNG-7FR5LQWC-T Japan Society for the Promotion of Science - No. 25461376 ArticleID:JCB25088 istex:792D5E0985AD7818B83F709B9269F4E542D32473 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0730-2312 1097-4644 |
DOI: | 10.1002/jcb.25088 |