BMP signaling balances proliferation and differentiation of muscle satellite cell descendants.
BMP signaling balances proliferation and differentiation of muscle satellite cell descendants.
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DOI：
10.1186/1471-2121-12-26
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发表时间：
2011-06-06
期刊：
影响因子：
--
通讯作者：
Vortkamp A
中科院分区：
文献类型：
--
作者：
Friedrichs M;Wirsdöerfer F;Flohé SB;Schneider S;Wuelling M;Vortkamp A
肌肉生长或损伤后再生的能力是由成体干细胞提供的，所谓的卫星细胞，位于每个肌纤维的基底层下。在激活时，卫星细胞进入细胞周期，增殖并分化成成肌细胞，其融合到受损的肌纤维或形成新的纤维。这些过程受到许多生长因子的严格控制。在这里，我们调查的作用，骨形态发生蛋白（BMPs）在卫星细胞分化。与肌源性C2C12细胞系不同，原代卫星细胞在BMP信号传导后不分化成成骨细胞。相反，BMP信号传导抑制离体原代卫星细胞的肌源性分化。相反，BMP信号传导的抑制导致细胞周期退出，随后是增强的成肌细胞分化和肌管形成。使用体内创伤模型，我们证明了卫星细胞在再生过程中对BMP信号作出反应。有趣的是，我们发现BMP抑制剂Chordin在原代卫星细胞培养物和再生肌肉中上调。在这两种系统中，Chordin的表达遵循Myogenin的表达，Myogenin是细胞分化的标志物。我们的数据表明，BMP信号在平衡活化的卫星细胞及其后代的增殖和分化中起着关键作用。最初，BMP信号维持卫星细胞后代处于增殖状态，从而扩大细胞数量。在细胞定向分化后，它们上调BMP抑制剂Chordin的表达，从而以负反馈机制支持终末分化和肌管形成。
The capacity of muscle to grow or to regenerate after damage is provided by adult stem cells, so called satellite cells, which are located under the basement lamina of each myofiber. Upon activation satellite cells enter the cell cycle, proliferate and differentiate into myoblasts, which fuse to injured myofibers or form new fibers. These processes are tightly controlled by many growth factors. Here we investigate the role of bone morphogenetic proteins (BMPs) during satellite cell differentiation. Unlike the myogenic C2C12 cell line, primary satellite cells do not differentiate into osteoblasts upon BMP signaling. Instead BMP signaling inhibits myogenic differentiation of primary satellite cells ex vivo. In contrast, inhibition of BMP signaling results in cell cycle exit, followed by enhanced myoblast differentiation and myotube formation. Using an in vivo trauma model we demonstrate that satellite cells respond to BMP signals during the regeneration process. Interestingly, we found the BMP inhibitor Chordin upregulated in primary satellite cell cultures and in regenerating muscles. In both systems Chordin expression follows that of Myogenin, a marker for cells committed to differentiation. Our data indicate that BMP signaling plays a critical role in balancing proliferation and differentiation of activated satellite cells and their descendants. Initially, BMP signals maintain satellite cells descendants in a proliferating state thereby expanding cell numbers. After cells are committed to differentiate they upregulate the expression of the BMP inhibitor Chordin thereby supporting terminal differentiation and myotube formation in a negative feedback mechanism.
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