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

描述（由申请方提供）：骨骼肌质量损失具有临床重要性，因为它与发病率和死亡率增加以及生活质量显著恶化相关。广泛的患者群体受到肌肉质量的显著损失的影响，包括那些患有各种全身性疾病（癌症、败血症、HIV- AIDS）、由于长期卧床、类风湿性关节炎和肢体固定导致的慢性身体活动不足、以及肌肉减少症（与年龄相关的肌肉质量和力量损失）的患者。卫星细胞目前是一个有吸引力的治疗目标，因为它们的干细胞特性和在出生后肌肉生长和再生中的重要作用。目前仍有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，萎缩后的再生长和衰老时的肌肉维持。为了解决这一根本问题，创建了一种新的小鼠品系，其能够特异性消融成熟骨骼肌中的卫星细胞。Pax 7-DTA小鼠将用于研究骨骼肌肥大（Aim 1）和肌肉萎缩后再生长（Aim 2）中卫星细胞的生理功能。从拟议的实验的结果预计将提供关于卫星细胞在成人骨骼肌可塑性的功能的基础知识，这将有助于确定卫星细胞在治疗各种临床条件下的肌肉质量损失的治疗价值。 公共卫生相关性：肌肉损失是与许多慢性疾病、缺乏体力活动或衰老相关的常见症状，对一个人的生活质量产生负面影响，增加了对其他疾病并发症的易感性，甚至可能导致死亡。旨在恢复或预防肌肉损失的治疗部分集中在使用被称为卫星细胞的肌肉干细胞。这项研究的目的是确定卫星细胞是否是成人肌肉生长所必需的，因此是骨骼肌损失治疗的适当靶点。

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.