Muscle-bone interactions in dystrophin-deficient and myostatin-deficient mice.
Muscle-bone interactions in dystrophin-deficient and myostatin-deficient mice.
复制标题
DOI：
10.1002/ar.a.20224
复制
发表时间：
2005-09
期刊：
影响因子：
--
通讯作者：
E. Montgomery;C. Pennington;C. Isales;M. Hamrick
中科院分区：
文献类型：
--
作者：
E. Montgomery;C. Pennington;C. Isales;M. Hamrick
我们利用两种已知在骨骼肌生长和发育方面不同于正常小鼠的小鼠突变体研究了肌肉与骨骼的相互作用：缺乏肌肉生长抑制素（GDF8）的小鼠和缺乏肌营养不良蛋白（mdx）的小鼠。与正常小鼠相比，肌生成抑制素缺乏小鼠的肌肉大小和力量增加，而mdx小鼠是杜氏肌营养不良症的一种成熟的动物模型。mdx小鼠后肢肌肉明显大于对照组，股四头肌的组织学切片显示营养不良变化，伴有广泛的纤维化。mdx小鼠的股骨骨密度（BMD）和骨折强度（Fu）明显高于对照组，这些变量与股四头肌质量的相关性比与体重的相关性更强。相反，与对照组相比，mdx小鼠脊柱的骨密度不高，而与正常小鼠相比，肌生成抑制素缺乏小鼠腰椎的骨密度显著增加。与正常小鼠相比，mdx小鼠和肌抑制素缺乏小鼠的股骨粗转子均扩大，以附着后肢大肌肉，并且两种突变株均表现出中外侧惯性横截面积矩（Iyy）增加，而正后部惯性矩（Ixx）没有增加。这些数据表明，瘦（肌肉）质量是四肢骨骼骨矿物质密度和强度的重要决定因素，即使伴有营养不良表型。同样，肌肉量的增加会导致肌肉附着部位的外部尺寸显著增加，即使肌肉量的增加伴随着广泛的纤维化和肌肉无力。
We have investigated muscle-bone interactions using two mouse mutants that are known to differ from normal mice in skeletal muscle growth and development: mice lacking myostatin (GDF8) and mice lacking dystrophin (mdx). Myostatin-deficient mice show increased muscle size and strength compared to normal mice, whereas the mdx mouse is a well-established animal model for Duchenne muscular dystrophy. The mdx mice have significantly larger hindlimb muscles than controls, and histological sections of the quadriceps muscles show dystrophic changes with extensive fibrosis. Femoral bone mineral density (BMD) and fracture strength (Fu) are significantly greater in mdx mice than controls, and these variables are more strongly correlated with quadriceps muscle mass than with body mass. In contrast, mdx mice do not shower high bone mineral density in the spine relative to controls, whereas myostatin-deficient mice have significantly increased BMD in the lumbar spine compared to normal mice. Both mdx mice and myostatin-deficient mice have expanded femoral trochanters for attachment of large hindlimb muscles, and both mutant strains show increased cross-sectional area moments of inertia mediolaterally (Iyy) but not anteroposteriorly (Ixx) compared to normal mice. These data suggest that lean (muscle) mass is a significant determinant of bone mineral density and strength in the limb skeleton, even when accompanied by a dystrophic phenotype. Likewise, increased muscle mass produces a marked increase in the external dimensions of muscle attachment sites, even when increased muscle size is accompanied by extensive fibrosis and muscle weakness.