The role of satellite cells in adult skeletal muscle growth and maintenance

描述（由申请人提供）：骨骼肌质量的丧失具有重要的临床意义，因为它与发病率和死亡率的增加以及生活质量的显着恶化有关。广泛的患者群体受到肌肉质量显著减少的影响，包括那些患有各种全身性疾病（癌症、败血症、艾滋病毒-艾滋病）、长期卧床休息导致的慢性身体活动不足、类风湿关节炎和肢体固定以及肌肉减少症（与年龄相关的肌肉质量和力量减少）的患者。鉴于卫星细胞的干细胞特性和在产后肌肉生长和再生中的重要作用，目前卫星细胞是一个有吸引力的治疗靶点。卫星细胞在肌肉可塑性的其他方面的必要性，如肥大、萎缩后的再生长和衰老后的肌肉维持，仍然存在争议。为了解决这个基本问题，一种新的小鼠品系被创造出来，它能够特异性地消融成熟骨骼肌中的卫星细胞。Pax7-DTA小鼠将用于研究卫星细胞在骨骼肌肥大（Aim 1）和肌肉萎缩后再生长（Aim 2）中的生理功能。这些实验的结果有望为卫星细胞在成人骨骼肌可塑性中的功能提供基础知识，这将有助于确定卫星细胞在治疗各种临床条件下肌肉质量损失的治疗价值。

DESCRIPTION (provided by applicant): The loss of skeletal muscle mass is of clinical importance because it is associated with increased morbidity and mortality, as well as a marked deterioration in the quality of life. A broad patient population is affected by significant losses in muscle mass including those afflicted by various systemic diseases (cancer, sepsis, HIV- AIDS), chronic physical inactivity as a result of long term bed rest, rheumatoid arthritis and limb immobilization, and sarcopenia, the age associated loss in muscle mass and strength. Satellite cells are currently an attractive therapeutic target given their stem cell characteristics and essential role in post-natal muscle growth and regeneration. What remains controversial is the necessity of satellite cells in other aspects of muscle plasticity such as hypertrophy, re-growth following atrophy and muscle maintenance with aging. In an effort to resolve this fundamental issue, a novel mouse line was created which enables the specific ablation of satellite cells in mature skeletal muscle. The Pax7-DTA mouse will be used to investigate the physiological function of satellite cells in skeletal muscle hypertrophy (Aim 1) and re-growth following muscle atrophy (Aim 2). The results from the proposed experiments are expected to provide fundamental knowledge on the function of satellite cells in adult skeletal muscle plasticity which will help define the therapeutic value of satellite cells in treating the loss of muscle mass in various clinical conditions.