Effective fiber hypertrophy in satellite cell-depleted skeletal muscle
Effective fiber hypertrophy in satellite cell-depleted skeletal muscle
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DOI：
10.1242/dev.068858
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发表时间：
2011-09-01
期刊：
影响因子：
4.6
通讯作者：
Peterson, Charlotte A.
中科院分区：
文献类型：
--
作者：
McCarthy, John J.;Mula, Jyothi;Peterson, Charlotte A.
骨骼肌可塑性中一个重要的悬而未决的问题是，卫星细胞是否是肌肉纤维肥大所必需的。为了解决这个问题，一种新的小鼠品系(Pax7-DTA)被创造出来，它能够在给药后有条件地消融成熟骨骼肌中90%的卫星细胞。为了验证卫星细胞是骨骼肌肥大所必需的假说，成年Pax7-DTA小鼠的足底肌用手术切除增效肌的方法承受机械超负荷。在两周的超负荷后，卫星细胞耗竭的肌肉显示出与赋形剂治疗组相同的肌肉质量(大约两倍)和纤维横截面积的增加和肥大。伴随肥大的典型肌核增加在卫星细胞耗尽的纤维中不存在，导致肌核结构域扩张。长期BrdU标记显示，卫星细胞耗竭的肌肉中BrdU阳性肌核的数量与载体处理的肌肉相比显著减少，这与扩大的纤维缺乏核的存在是一致的。单纤维功能分析显示，车用和三苯氧胺处理组肥大纤维的比力、钙敏感性、跨桥循环率和协同性均无差异。虽然这是肥大反应的一小部分，但在卫星细胞耗尽后，纤维的增殖和再生都明显减弱，这表明在这些过程中对卫星细胞有明显的需求。这些结果提供了令人信服的证据，表明骨骼肌纤维能够对机械超负荷产生强大的肥大反应，而不依赖于卫星细胞。
An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca2+ sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.