Muscle hypertrophy and the regenerative potential in skeletal muscles induced by the activation of tissue-specific stem

骨骼肌对外界刺激的反应具有很大的可塑性。骨骼肌特异性干细胞，即卫星细胞，在骨骼肌的可塑性中起着重要作用。卫星细胞的激活不仅发生在受损骨骼肌的再生过程中，也发生在萎缩骨骼肌的再生过程中。因此，卫星细胞的激活可以防止肌肉萎缩，以应对老化，不活动和废用。本研究的目的是阐明卫星细胞在骨骼肌再生潜力中的作用和来源，并研究损伤和未损伤骨骼肌再生潜力的调节因素。本研究的主要结果为：1）肥大刺激可促进骨骼肌损伤后的再生过程，2）骨髓干细胞可能参与骨骼肌损伤后的再生过程，3）热应激、雌激素和机械应力刺激细胞内信号，增强骨骼肌损伤后的再生潜能，（4）热休克蛋白72的表达上调，刺激细胞内信号，导致骨骼肌肥大。有证据表明，应激反应相关的细胞内和细胞外信号可以通过激活肌肉卫星细胞以及刺激其他干细胞来源的干细胞动员来增强骨骼肌的再生潜力。这些证据对运动科学和康复医学中肌肉萎缩的对策、肌肉肥大的特异性治疗方法和促进骨骼肌损伤再生的康复技术的发展具有重要意义。

Skeletal muscles have a large plasticity in response to external stimuli. Skeletal muscle-specific stem cells, so-called satellite cells, play an important role in the plasticity of skeletal muscles. The activation of satellite cells occurs during not only the regeneration of injured skeletal muscles but also the regrowth of atrophied skeletal muscles. Therefore, the activation of satellite cells could prevent muscle atrophy in response to aging, an inactivity and a disuse. The purpose of the present study was to elucidate the role(s) and the source of satellite cells in the regenerative potential of the skeletal muscles and to investigate the regulatory factors for the regenerative potential of injured and uninjured skeletal muscles. The main results of the present study as fellow ; 1) hypertrophic stimuli could facilitates the regenerative process of injured skeletal muscles, 2) bone marrow stem cells may participate in the regeneration of injured skeletal muscles, 3) the intracellular signals, which enhanced the regenerative potential, were stimulated by heat-stress, estrogen and mechanical stress, 4) the up-regulation of heat shock protein 72 would stimulate the intracellular signals, which induced skeletal muscle hypertrophy. Evidences strongly suggest that stress response-associated intracellular as well as extracellular signals could enhance the regenerative potential of skeletal muscles via the activation of muscle satellite cells as well as the stimulation of the mobilization of stem cells from other stem cells sources. These evidences may be useful for the developments of the countermeasures for muscle atrophy, the specific method for muscle hypertrophy, and the rehabilitation technique to facilitate the regeneration of injured skeletal muscles in sports sciences as well as rehabilitation medicine.