The myogenic factor Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification
The myogenic factor Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification
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DOI：
10.1634/stemcells.2006-0736
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发表时间：
2007-08-01
期刊：
影响因子：
5.2
通讯作者：
Braun, Thomas
中科院分区：
文献类型：
--
作者：
Ustanina, Svetlana;Carvajal, Jaime;Braun, Thomas
肌肉生成因子Myf5定义了哺乳动物在发育过程中肌肉发生的开始。同时缺乏Myf5和MyoD的小鼠无法形成成肌细胞，其特征是出生时骨骼肌完全缺失。为了研究Myf5在成人骨骼肌中的功能，我们构建了具有持续再生特性的Myf5和MDX复合突变体。双突变小鼠表现出肌肉营养不良改变的增加，尽管这些小鼠是存活的，并且肌病的程度不是很严重。Myf5突变肌肉的卫星细胞数量略有减少，在生理变异范围内。我们还观察到，损伤后Myf5缺陷骨骼肌的再生明显延迟。有趣的是，Myf5缺陷的骨骼肌能够在再生过程中消除这种缺陷，在受伤4周后产生完整的肌肉。虽然我们没有发现在再生肌肉中MyoD阳性激活的成肌细胞或Myf5-LacZ阳性细胞显著减少，但卫星细胞来源的成肌细胞的增殖率在卫星细胞来源的培养中明显降低。Myf5突变型成肌细胞增殖率的下降也反映在从增殖到分化的延迟，导致培养6天和7天的肌管核数量减少。我们认为，Myf5通过瞬间扩增成肌细胞来支持高效的骨骼肌再生。
The myogenic factor Myf5 defines the onset of myogenesis in mammals during development. Mice lacking both Myf5 and MyoD fail to form myoblasts and are characterized by a complete absence of skeletal muscle at birth. To investigate the function of Myf5 in adult skeletal muscle, we generated Myf5 and mdx compound mutants, which are characterized by constant regeneration. Double mutant mice show an increase of dystrophic changes in the musculature, although these mice were viable and the degree of myopathy was modest. Myf5 mutant muscles show a small decrease in the number of muscle satellite cells, which was Within the range of physiological variations. We also observed a significant delay in the regeneration of Myf5 deficient skeletal muscles after injury. Interestingly, Myf5 deficient skeletal muscles were able to even out this flaw during the course of regeneration, generating intact muscles 4 weeks after injury. Although we did not detect a striking reduction of MyoD positive activated myoblasts or of Myf5-LacZ positive cells in regenerating muscles, a clear decrease in the proliferation rate of satellite cell-derived myoblasts was apparent in satellite cell-derived cultures. The reduction of the proliferation rate of Myf5 mutant myoblasts was also reflected by a delayed transition from proliferation to differentiation, resulting in a reduced number of myotube nuclei after 6 and 7 days of culture. We reason that Myf5 supports efficient skeletal muscle regeneration by enabling transient myoblast amplification.