Shefer G, Carmeli E, Rauner G, Yablonka-Reuveni Z, Benayahu D
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
J Cell Physiol. 2008 Apr;215(1):265-75. doi: 10.1002/jcp.21306.
Prolonged limb immobilization, which is often the outcome of injury and illness, results in the atrophy of skeletal muscles. The basis of muscle atrophy needs to be better understood in order to allow development of effective countermeasures. The present study focused on determining whether skeletal muscle stem cells, satellite cells, are directly affected by long-term immobilization as well as on investigating the potential of pharmacological and physiological avenues to counterbalance atrophy-induced muscle deterioration. We used external fixation (EF), as a clinically relevant model, to gain insights into the relationships between muscle degenerative and regenerative conditions to the myogenic properties and abundance of bona fide satellite cells. Rats were treated with tetracycline (Tet) through the EF period, or exercise trained on a treadmill for 2 weeks after the cessation of the atrophic stimulus. EF induced muscle mass loss; declined expression of the muscle specific regulatory factors (MRFs) Myf5, MyoD, myogenin, and also of satellite cell numbers and myogenic differentiation aptitude. Tet enhanced the expression of MRFs, but did not prevent the decline of the satellite cell pool. After exercise running, however, muscle mass, satellite cell numbers (enumerated through the entire length of myofibers), and myogenic differentiation aptitude (determined by the lineal identity of clonal cultures of satellite cells) were re-gained to levels prior to EF. Together, our results point to Tet and exercise running as promising and relevant approaches for enhancing muscle recovery after atrophy.
肢体长期固定通常是伤病的结果，会导致骨骼肌萎缩。为了开发有效的应对措施，需要更好地理解肌肉萎缩的基础。本研究重点在于确定骨骼肌干细胞即卫星细胞是否会受到长期固定的直接影响，以及研究通过药理学和生理学途径来平衡萎缩引起的肌肉退化的潜力。我们使用外固定（EF）作为一种临床相关模型，以深入了解肌肉退化和再生状况与真正卫星细胞的成肌特性和数量之间的关系。大鼠在EF期间接受四环素（Tet）治疗，或在萎缩刺激停止后在跑步机上进行2周的运动训练。EF导致肌肉质量损失；肌肉特异性调节因子（MRFs）Myf5、MyoD、肌细胞生成素的表达下降，卫星细胞数量和生肌分化能力也下降。Tet增强了MRFs的表达，但并未阻止卫星细胞池的减少。然而，运动跑步后，肌肉质量、卫星细胞数量（通过肌纤维全长计数）和生肌分化能力（由卫星细胞克隆培养物的线性特征确定）恢复到EF之前的水平。总之，我们的结果表明，Tet和运动跑步是促进萎缩后肌肉恢复的有前景且相关的方法。
