Development of Arterial Calcification in Adiponectin-Deficient Mice: Adiponectin Regulates Arterial Calcification
Development of Arterial Calcification in Adiponectin-Deficient Mice: Adiponectin Regulates Arterial Calcification
复制标题
脂联素缺陷小鼠动脉钙化的发展：脂联素调节动脉钙化
DOI：
10.1359/jbmr.090227
复制
发表时间：
2009-08-01
影响因子：
6.2
通讯作者：
Liao, Er-Yuan
中科院分区：
文献类型：
--
作者：
Luo, Xiang-Hang;Zhao, Li-Ling;Liao, Er-Yuan
动脉钙化很常见，但其机制尚不清楚。本研究旨在探讨脂联素缺乏小鼠体内动脉钙化及脂联素对体外培养血管平滑肌细胞的影响。采用茜素红S染色检测脂联素（-/-）小鼠动脉钙化情况。检测培养钙化血管平滑肌细胞（CVSMCs）碱性磷酸酶活性、骨钙素分泌及Runx2蛋白表达。利用丝裂原活化蛋白激酶（MAPK）抑制剂和脂联素受体1 (AdipoR1) siRNA研究了相关信号通路。脂联素（-/-）小鼠在正常鼠粮喂养30周后出现轻微动脉钙化。腺病毒介导的脂联素补充减轻了这些小鼠的动脉钙化。在培养的CVSMCs中，脂联素抑制ALP活性、骨钙素分泌、Runx2蛋白表达和矿化结节的形成。在CVSMCs中检测到脂联素受体1 （AdipoR1）蛋白，脂联素激活p38丝裂原活化蛋白激酶。此外，抑制AdipoR1表达或p38激活逆转了脂联素对ALP活性的影响。上述结果表明，脂联素通过AdipoR1/p38信号通路抑制CVSMCs成骨分化。我们的研究结果表明，脂联素（-/-）小鼠出现动脉钙化，这可能归因于脂联素对CVSMCs成骨分化的抑制作用丧失。这表明脂联素对动脉钙化具有保护作用。[J]中华骨科学杂志，2009;24(4):661 - 668。2009年2月16日在线发布；doi: 10.1359 / JBMR.090227
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 ostcoblastic differentiation of CVSMCs. It suggested that adiponectin plays a protective role against arterial calcification. J Bone Miner Res 2009;24:1461-1468. Published online on February 16, 2009; doi: 10.1359/JBMR.090227