Abortive myogenesis in denervated skeletal muscle: differentiative properties of satellite cells, their migration, and block of terminal differentiation
Abortive myogenesis in denervated skeletal muscle: differentiative properties of satellite cells, their migration, and block of terminal differentiation
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DOI：
10.1007/s00429-004-0429-7
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发表时间：
2005-04-01
期刊：
影响因子：
--
通讯作者：
Carlson, BM
中科院分区：
文献类型：
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作者：
Borisov, AB;Dedkov, EI;Carlson, BM
关于去神经后肌肉萎缩期间生肌卫星细胞的生物学特性知之甚少。本研究调查了卫星细胞的分化能力及其在长期去神经大鼠肌肉的代偿性再生过程中的参与。去神经后1-18个月的肌肉组织的电子显微镜和免疫细胞化学标记表明，尽管卫星细胞被激活，但去神经肌肉中的肌生成是失败的并且不会导致正常肌纤维的形成。新形成的去神经肌管尺寸小、收缩系统发育不良以及表面缺乏卫星细胞表明它们的分化通常不会进展到终末阶段。许多未成熟的肌管会退化，而另一些则存活下来，但嵌入其母体纤维附近的胶原蛋白晶格中。有趣的是，位于基底层下方母体肌纤维表面上的新形成的肌管通常不包含发达的肌原纤维。这表明子代和亲代肌纤维的接触阻止了肌原纤维的形成。在大多数情况下，肌节的组装发生在子代肌纤维和亲代肌纤维完全空间分离之后。肌源性前体参与流产肌发生的另一个表现是形成被共同基底层包围的不发达的分支肌管簇。我们发现成肌细胞也可以直接与分化的肌纤维融合。基底层开口附近和间隙空间中卫星细胞的存在表明肌源性前体细胞可以迁移通过基底层并在距母体纤维一定距离处形成肌管。我们的数据可以解释为什么长期失神经的骨骼肌再生和功能恢复能力较差。
Little is known about the biological properties of myogenic satellite cells during postdenervation muscle atrophy. The present study investigated the differentiative capacity of satellite cells and their involvement in the compensatory regenerative process in long-term denervated rat muscle. Electron microscopy and immunocytochemical labeling of muscle tissue 1-18 months following denervation demonstrated that despite activation of satellite cells, myogenesis in denervated muscle is abortive and does not lead to the formation of normal muscle fibers. Small sizes, poor development of the contractile system in newly formed denervated myotubes, and the absence of satellite cells on the surface indicate that their differentiation typically does not progress to terminal stages. Many immature myotubes degenerate, and others survive but are embedded in a collagen lattice near their parent fibers. Interestingly, newly formed myotubes located on the surface of parent muscle fibers beneath the basal lamina typically did not contain developed myofibrils. This suggests that the contacts of daughter and parent muscle fibers block myofibrillogenesis. Assembly of sarcomeres in most cases occurs following complete spatial separation of daughter and parent muscle fibers. Another manifestation of the involvement of myogenic precursors in abortive myogenesis is the formation of clusters of underdeveloped branching myotubes surrounded by a common basal lamina. We found that myoblasts can also fuse directly with differentiated muscle fibers. The presence of satellite cells near the openings in the basal lamina and in the interstitial space indicates that myogenic precursors can migrate through the basal lamina and form myotubes at a distance from parent fibers. Our data may explain why long-term denervated skeletal muscle has a poor capacity for regeneration and functional restoration.