Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice
Stanniocalcin 1 alters muscle and bone structure and function in transgenic mice
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DOI：
10.1210/en.2001-211424
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发表时间：
2002-09-01
期刊：
影响因子：
4.8
通讯作者：
French, DM
中科院分区：
文献类型：
--
作者：
Filvaroff, EH;Guillet, S;French, DM
鱼斯钙素（STC）抑制钙的吸收和刺激磷酸盐重吸收。为了确定高度同源的哺乳动物蛋白质STC-1的作用，我们创建并表征了在肌肉特异性启动子控制下表达STC-1的转基因小鼠。STC-1转基因小鼠比野生型同窝小鼠小，生长板软骨形态正常，但软骨基质合成增加。在STC-1小鼠中，骨形成率下降，但骨矿化率没有下降。STC-1小鼠皮质骨厚度增加和骨小梁数量、密度和厚度的变化表明破骨细胞活性同时受到抑制，这得到了显微计算机断层扫描分析和组织化学的支持。在STC-1小鼠中，骨骼肌不成比例地小，并且显示出改变的功能和对损伤的反应。电子显微镜观察表明，STC-1小鼠的肌肉线粒体显着增大。STC-1小鼠的这些变化不能用血管形成缺陷来解释，因为器官和骨骼组织中的血管分布增加，因为股动脉结扎引起血管分布诱导。我们的研究结果表明，STC-1可以影响钙稳态，骨和肌肉的质量和结构，并通过对成骨细胞，破骨细胞，成肌细胞/肌细胞和内皮细胞的影响血管生成。
Fish stanniocalcin (STC) inhibits uptake of calcium and stimulates phosphate reabsorption. To determine the role of the highly homologous mammalian protein, STC-1, we created and characterized transgenic mice that express STC-1 under control of a muscle-specific promoter. STC-1 transgenic mice were smaller than wild-type littermates and had normal growth plate cartilage morphology but increased cartilage matrix synthesis. In STC-1 mice, the rate of bone formation, but not bone mineralization, was decreased. Increased cortical bone thickness and changes in trabeculae number, density, and thickness in STC-1 mice indicated a concomitant suppression of osteoclast activity, which was supported by microcomputed tomography analyses and histochemistry. Skeletal muscles were disproportionately small and showed altered function and response to injury in STC-1 mice. Electron microscopy indicated that muscle mitochondria were dramatically enlarged in STC-1 mice. These changes in STC-1 mice could not be explained by deficits in blood vessel formation, as vascularity in organs and skeletal tissues was increased as was induction of vascularity in response to femoral artery ligation. Our results indicate that STC-1 can affect calcium homeostasis, bone and muscle mass and structure, and angiogenesis through effects on osteoblasts, osteoclasts, myoblasts/myocytes, and endothelial cells.