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Development of Arterial Calcification in Adiponectin‐Deficient Mice: Adiponectin Regulates Arterial Calcification
Author(s) -
Luo XiangHang,
Zhao LiLing,
Yuan LingQing,
Wang Min,
Xie Hui,
Liao ErYuan
Publication year - 2009
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.090227
Subject(s) - adiponectin , medicine , endocrinology , osteocalcin , adiponectin receptor 1 , calcification , osteoprotegerin , runx2 , chemistry , vascular smooth muscle , osteopontin , osteoblast , biology , alkaline phosphatase , receptor , in vitro , biochemistry , insulin resistance , activator (genetics) , smooth muscle , insulin , enzyme
Arterial calcification is common, but the mechanisms remain unclear. This study was undertaken to investigate the arterial calcification in adiponectin‐deficient mice in vivo and the effects of adiponectin on cultured vascular smooth muscle cells in vitro. Alizarin red S staining was used to detect arterial calcification of adiponectin −/− mice. Alkaline phosphatase activity, osteocalcin secretion, and Runx2 protein expression were examined in cultured calcifying vascular smooth muscle cells (CVSMCs). The involved signal pathway was studied using a mitogen‐activated protein kinase (MAPK) inhibitor and adiponectin receptor 1 (AdipoR1) siRNA. Adiponectin −/− mice developed slight arterial calcification after being fed with normal chow diet for 30 wk. Adenovirus‐mediated supplement of adiponectin attenuated arterial calcification in these mice. On cultured CVSMCs, adiponectin inhibited ALP activity, osteocalcin secretion, Runx2 protein expression, and the formation of mineralized nodules. Adiponectin receptor 1 (AdipoR1) protein was detected in CVSMCs, and adiponectin activated p38 mitogen‐activated protein kinase. Furthermore, inhibition of AdipoR1 expression or p38 activation reversed the effects of adiponectin on ALP activity. These results showed that adiponectin inhibited osteoblastic differentiation of CVSMCs through the AdipoR1/p38 signaling pathway. Our findings showed that adiponectin −/− mice developed arterial calcification, and this could be attributed to the loss of inhibitory action of adiponectin on osteoblastic differentiation of CVSMCs. It suggested that adiponectin plays a protective role against arterial calcification.