Satellite cell depletion does not inhibit adult skeletal muscle regrowth following unloading-induced atrophy
Satellite cell depletion does not inhibit adult skeletal muscle regrowth following unloading-induced atrophy
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DOI：
10.1152/ajpcell.00207.2012
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发表时间：
2012-10-01
影响因子：
5.5
通讯作者：
Dupont-Versteegden, Esther E.
中科院分区：
文献类型：
--
作者：
Jackson, Janna R.;Mula, Jyothi;Dupont-Versteegden, Esther E.
杰克逊JR，穆拉J，Kirby TJ，Fry CS，Lee JD，Ubele MF，坎贝尔KS，McCarthy JJ，Peterson CA，Dupont-Versteegden EE.卫星细胞耗竭不会抑制卸载诱导萎缩后的成人骨骼肌再生。Am J Physiol Cell Physiol 303：C854-C861，2012。首次发表于2012年8月15日; doi：10.1152/ajpcell.00207.2012.-常驻肌肉干细胞，被称为卫星细胞，被认为是骨骼肌可塑性的主要介质。卫星细胞被激活，复制，并融合到现有的肌肉纤维，以响应肌肉损伤和机械负荷。卫星细胞参与出生后的生长、肥大和损伤后的肌肉再生是公认的;然而，它们在萎缩刺激后的肌肉再生中的作用仍然是不明确的。目前的研究采用了一种遗传小鼠模型（Pax 7-DTA），该模型允许在施用他莫昔芬后有效消耗成人肌肉中>90%的卫星细胞。将溶剂和他莫昔芬处理的年轻成年雌性小鼠后肢悬吊14天以诱导肌肉萎缩，或后肢悬吊14天，然后重新加载14天以允许再生长，或在实验方案期间保持行走。此外，将5-溴-2 '-脱氧尿苷（BrdU）添加到饮用水中以跟踪细胞增殖。比目鱼肌萎缩，作为衡量整个肌肉湿重，纤维横截面积，和单纤维宽度，发生在响应悬浮液和卫星细胞耗尽和控制肌肉之间没有差异。此外，在14天的重新加载期间，卫星细胞的消耗并没有减弱肌肉质量或力量恢复，这表明卫星细胞不是肌肉再生所必需的。在悬浮或重新加载期间，在来自载体处理或卫星细胞耗尽的动物的比目鱼肌肌纤维中，肌纤维数量没有改变。因此，肌球蛋白结构域的大小减少悬浮后，由于减少的细胞质体积，并完全恢复后重新加载，独立的卫星细胞的存在。这些结果提供了令人信服的证据，卫星细胞是不需要肌肉再生萎缩后，相反，肌纤维适应的肌纤维结构域的大小变化。
Jackson JR, Mula J, Kirby TJ, Fry CS, Lee JD, Ubele MF, Campbell KS, McCarthy JJ, Peterson CA, Dupont-Versteegden EE. Satellite cell depletion does not inhibit adult skeletal muscle regrowth following unloading-induced atrophy. Am J Physiol Cell Physiol 303: C854-C861, 2012. First published August 15, 2012; doi:10.1152/ajpcell.00207.2012.-Resident muscle stem cells, known as satellite cells, are thought to be the main mediators of skeletal muscle plasticity. Satellite cells are activated, replicate, and fuse into existing muscle fibers in response to both muscle injury and mechanical load. It is generally well-accepted that satellite cells participate in postnatal growth, hypertrophy, and muscle regeneration following injury; however, their role in muscle regrowth following an atrophic stimulus remains equivocal. The current study employed a genetic mouse model (Pax7-DTA) that allowed for the effective depletion of >90% of satellite cells in adult muscle upon the administration of tamoxifen. Vehicle and tamoxifen-treated young adult female mice were either hindlimb suspended for 14 days to induce muscle atrophy or hindlimb suspended for 14 days followed by 14 days of reloading to allow regrowth, or they remained ambulatory for the duration of the experimental protocol. Additionally, 5-bromo-2'-deoxyuridine (BrdU) was added to the drinking water to track cell proliferation. Soleus muscle atrophy, as measured by whole muscle wet weight, fiber cross-sectional area, and single-fiber width, occurred in response to suspension and did not differ between satellite cell-depleted and control muscles. Furthermore, the depletion of satellite cells did not attenuate muscle mass or force recovery during the 14-day reloading period, suggesting that satellite cells are not required for muscle regrowth. Myonuclear number was not altered during either the suspension or the reloading period in soleus muscle fibers from vehicle-treated or satellite cell-depleted animals. Thus, myonuclear domain size was reduced following suspension due to decreased cytoplasmic volume and was completely restored following reloading, independent of the presence of satellite cells. These results provide convincing evidence that satellite cells are not required for muscle regrowth following atrophy and that, instead, the myonuclear domain size changes as myofibers adapt.