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

描述(由申请人提供)：骨骼肌块的减少具有临床重要性，因为它与发病率和死亡率的增加以及生活质量的显著恶化有关。广泛的患者群体受到肌肉质量显著下降的影响，包括各种系统性疾病(癌症、败血症、艾滋病毒/艾滋病)、长期卧床导致的慢性体力活动不足、类风湿性关节炎和肢体瘫痪，以及与年龄相关的肌肉质量和力量丧失。鉴于卫星细胞的干细胞特性和在出生后肌肉生长和再生中的重要作用，卫星细胞目前是一个有吸引力的治疗靶点。仍然存在争议的是卫星细胞在肌肉可塑性的其他方面的必要性，如肥大、萎缩后的重新生长和肌肉随着年龄的增长而维持。为了解决这一根本问题，创造了一种新的小鼠品系，它能够特异性地消融成熟骨骼肌中的卫星细胞。Pax7-DTA小鼠将被用来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。这些实验结果有望为卫星细胞在成人骨骼肌可塑性中的作用提供基础知识，从而有助于确定卫星细胞在各种临床条件下治疗肌肉质量丧失的治疗价值。 公共卫生相关性：肌肉丧失是许多慢性病、缺乏运动或衰老的常见症状，对一个人的生活质量产生负面影响，增加对其他疾病并发症的易感性，甚至可能导致死亡。旨在恢复或防止肌肉丧失的治疗方法在一定程度上侧重于使用被称为卫星细胞的肌肉干细胞。这项拟议的研究的目标是确定卫星细胞是否是成人肌肉生长所必需的，从而是治疗骨骼肌丢失的合适靶点。

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. PUBLIC HEALTH RELEVANCE: Loss of muscle, a common symptom associated with many chronic diseases, physical inactivity or aging, negatively impacts a person's quality of life, increases the susceptibility to other complications of disease and can even lead to death. Treatments designed to restore or prevent muscle loss have in part focused on using muscle stem cells referred to as satellite cells. The goal of the proposed research is to determine if satellite cells are necessary for adult muscle growth and thus, are an appropriate target for therapy for skeletal muscle loss.