Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, 40536-0200, USA.
Am J Physiol Cell Physiol. 2012 Oct 15;303(8):C854-61. doi: 10.1152/ajpcell.00207.2012. Epub 2012 Aug 15.
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.
肌卫星细胞是一种存在于肌肉中的成体干细胞，被认为是骨骼肌可塑性的主要调节者。卫星细胞在受到肌肉损伤和机械负荷时被激活、复制并融合到现有的肌肉纤维中。人们普遍认为，卫星细胞参与了出生后的生长、肥大以及损伤后的肌肉再生；然而，它们在萎缩刺激后的肌肉再生长中的作用仍存在争议。本研究采用了一种遗传小鼠模型（Pax7-DTA），该模型在给予他莫昔芬后可有效耗竭成年肌肉中的>90%的卫星细胞。 vehicle 和 tamoxifen 处理的年轻成年雌性小鼠要么进行后肢悬吊 14 天以诱导肌肉萎缩，要么进行后肢悬吊 14 天再进行 14 天的再负荷以允许再生长，要么在整个实验过程中保持活动状态。此外，在饮用水中添加了 5-溴-2'-脱氧尿苷（BrdU）以跟踪细胞增殖。整个肌肉湿重、纤维横截面积和单纤维宽度的测量表明，比目鱼肌萎缩是对悬吊的反应，且在卫星细胞耗竭和对照肌肉之间没有差异。此外，卫星细胞的耗竭并没有在 14 天的再负荷期间减轻肌肉质量或力量的恢复，这表明卫星细胞不是肌肉再生长所必需的。在 vehicle 处理或卫星细胞耗竭动物的比目鱼肌纤维中，无论是在悬吊期间还是在再负荷期间，肌核数目都没有改变。因此，由于细胞质体积减少，肌核域大小在悬吊后减小，并在再负荷后完全恢复，与卫星细胞的存在无关。这些结果提供了令人信服的证据，表明卫星细胞不是肌肉萎缩后再生长所必需的，相反，肌核域大小的变化是肌纤维适应的结果。
