1Department of Kinesiology and Community Health, University of Illinois, Urbana, IL; 2Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana, IL; and 3Division of Biomedical Sciences, University of Illinois, Urbana, IL.
Med Sci Sports Exerc. 2015 Feb;47(2):315-25. doi: 10.1249/MSS.0000000000000405.
The α7β1 integrin is a transmembrane protein expressed in the skeletal muscle that can link the actin cytoskeleton to the surrounding basal lamina. We have previously demonstrated that transgenic mice overexpressing the α7B integrin in the skeletal muscle (MCK:α7B; α7Tg) mount an enhanced satellite cell and growth response to single or multiple bouts of eccentric exercise. In addition, interstitial stem cells characterized as mesenchymal stem cells (MSCs) accumulate in α7Tg muscle (mMSCs) in the sedentary state and after exercise. The results from these studies prompted us to determine the extent to which mMSC underlie the beneficial adaptive responses observed in α7Tg skeletal muscle after exercise.
mMSCs (Sca-1CD45) were isolated from α7Tg mice, dye-labeled, and intramuscularly injected into adult wild type recipient mice. After injection of mMSCs or saline, mice remained sedentary (SED) or were subjected to eccentric exercise training (TR) (downhill running) on a treadmill (three times per week) for 2 or 4 wk. Gastrocnemius-soleus complexes were collected 24 h after the last bout of exercise.
mMSCs did not directly fuse with existing fibers; however, mMSCs injection enhanced Pax7 satellite cell number and myonuclear content compared with all other groups at 2 wk after exercise. Mean CSA, percentage of larger caliber fibers (>3000 μm), and grip strength were increased in mMSCs/TR compared with saline/SED and mMSCs/SED at 4 wk. mMSC transplantation did not enhance repair or growth in the absence of exercise.
The results from this study demonstrate that mMSCs contribute to beneficial changes in satellite cell expansion and growth in α7Tg muscle after eccentric exercise. Thus, MSCs that naturally accumulate in the muscle after eccentric contractions may enhance the adaptive response to exercise.
α7β1 整合素是一种在骨骼肌中表达的跨膜蛋白，可将肌动蛋白细胞骨架与周围的基底膜连接起来。我们之前已经证明，在骨骼肌中过度表达α7B 整合素的转基因小鼠（MCK：α7B；α7Tg）对单次或多次离心运动表现出增强的卫星细胞和生长反应。此外，在静止状态和运动后，α7Tg 肌肉（mMSCs）中积累了间质干细胞特征的间充质干细胞（MSCs）。这些研究的结果促使我们确定 mMSC 在多大程度上为运动后α7Tg 骨骼肌观察到的有益适应性反应提供基础。
从α7Tg 小鼠中分离 mMSC（Sca-1CD45），染色标记，并肌肉内注射到成年野生型受体小鼠中。在注射 mMSC 或盐水后，小鼠保持静止（SED）或进行离心运动训练（TR）（在跑步机上下坡跑），每周三次，持续 2 或 4 周。在最后一次运动后 24 小时收集比目鱼肌-跟腱复合体。
mMSC 没有直接与现有纤维融合；然而，与所有其他组相比，mMSC 注射在运动后 2 周时增强了 Pax7 卫星细胞数量和肌核含量。与盐水/SED 和 mMSC/SED 相比，mMSC/TR 在 4 周时增加了平均 CSA、较大口径纤维（>3000μm）的百分比和握力。在没有运动的情况下，mMSC 移植不会增强修复或生长。
本研究结果表明，mMSC 有助于离心运动后α7Tg 肌肉卫星细胞扩张和生长的有益变化。因此，在离心收缩后自然积累在肌肉中的 MSC 可能增强对运动的适应性反应。
