Luo Xiang-Hang, Zhao Li-Ling, Yuan Ling-Qing, Wang Min, Xie Hui, Liao Er-Yuan
Institute of Endocrinology and Metabolism, The Second Xiangya Hospital of Central South University, Hunan, China
J Bone Miner Res. 2009 Aug;24(8):1461-8. 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 osteoblastic differentiation of CVSMCs. It suggested that adiponectin plays a protective role against arterial calcification.
动脉钙化很常见，但其机制尚不清楚。本研究旨在调查脂联素缺乏小鼠体内的动脉钙化情况以及脂联素对体外培养的血管平滑肌细胞的影响。采用茜素红S染色检测脂联素基因敲除（-/-）小鼠的动脉钙化情况。检测培养的钙化血管平滑肌细胞（CVSMCs）中的碱性磷酸酶活性、骨钙素分泌及Runx2蛋白表达。使用丝裂原活化蛋白激酶（MAPK）抑制剂和脂联素受体1（AdipoR1）小干扰RNA（siRNA）研究相关信号通路。脂联素基因敲除（-/-）小鼠在给予正常饲料喂养30周后出现轻微动脉钙化。腺病毒介导的脂联素补充可减轻这些小鼠的动脉钙化。在培养的CVSMCs上，脂联素抑制碱性磷酸酶活性、骨钙素分泌、Runx2蛋白表达及矿化结节的形成。在CVSMCs中检测到脂联素受体1（AdipoR1）蛋白，且脂联素激活p38丝裂原活化蛋白激酶。此外，抑制AdipoR1表达或p38激活可逆转脂联素对碱性磷酸酶活性的影响。这些结果表明，脂联素通过AdipoR1/p38信号通路抑制CVSMCs的成骨细胞分化。我们的研究结果表明，脂联素基因敲除（-/-）小鼠出现动脉钙化，这可能归因于脂联素对CVSMCs成骨细胞分化抑制作用的丧失。这表明脂联素在预防动脉钙化方面发挥保护作用。
