Role of osteoprotegerin in arterial calcification development of new animal model
Role of osteoprotegerin in arterial calcification development of new animal model
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DOI：
10.1161/atvbaha.107.147868
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发表时间：
2007-09-01
影响因子：
8.7
通讯作者：
Yoshizumi, Masao
中科院分区：
文献类型：
--
作者：
Orita, Yuichi;Yamamoto, Hideya;Yoshizumi, Masao
目的：破骨细胞生成增强，骨吸收增加，骨质疏松症已在骨保护素缺乏（-/-）小鼠中报道。在日本可用的OPG（-/-）小鼠通常不显示血管钙化。我们发现，在OPG（-/-）小鼠中，动脉钙化可以通过一个简单的程序快速诱导。方法与结果：雄性OPG（-/-）、OPG（+/-）和OPG（+/+）小鼠在出生后6 ~ 10周饲喂高磷饲料，然后注射1 α， 25-二羟基维生素D3（骨化三醇）3 d。我们发现，在OPG（-/-）小鼠的主动脉介质中发生了严重的钙化。电镜下，血管平滑肌细胞细胞质和细胞外基质中可见钙沉积。未见VSMCs凋亡，也未见巨噬细胞浸润。主动脉组织碱性磷酸酶（ALP）活性与钙化病变区域相关。小鼠主动脉和骨提取物经ALP电泳显示出相同的模式。结论：我们的结果表明，OPG在主动脉中具有抗钙化活性，可能是通过下调ALP活性来实现的。由于骨化三醇注射后动脉钙化的时间过程准确、可重复性好，该小鼠模型将为血管钙化的进一步研究提供参考。
Objectives-Enhanced osteoclastogenesis, increased bone resorption, and osteoporosis have been reported in osteoprotegerin-deficient ( OPG (-/-)) mice. OPG (-/-) mice available in Japan usually do not show vascular calcification. We have found that arterial calcification can be quickly induced by a simple procedure in OPG (-/-) mice.Methods and Results-Male OPG (-/-), OPG (+/-), and OPG (+/+) mice were fed a high phosphate diet from 6 to 10 weeks after birth, and then 1 alpha, 25-dihydroxyvitamin D3 ( calcitriol) was injected for 3 days. We found that severe calcification developed in the media of the aorta in OPG (-/-) mice. Under electron microscopy, calcium deposits were observed in the cytoplasm and extracellular matrix of vascular smooth muscle cells ( VSMCs). Neither apoptosis of VSMCs nor infiltration of macrophages was observed. Alkaline phosphatase ( ALP) activity of aortic tissue correlated with the calcified lesion area. Mouse aorta and bone extracts revealed an identical pattern by ALP electrophoresis.Conclusions-Our results demonstrated that OPG had anticalcification activity in the aorta, probably through the downregulation of ALP activity. Because the time course of arterial calcification after the injection of calcitriol is accurate and reproducible, this mouse model will be useful for further investigation of vascular calcification.