Rotator Cuff Degeneration and Repair

描述（由申请人提供）：肩部的肩袖肌肉提供肩关节的稳定性和运动。肩袖疾病是一种退行性疾病，可导致明显的肩部疼痛、肌肉萎缩和肌腱断裂，严重限制上肢功能。肩袖修复治疗肩痛和恢复力量是最常见的骨科手术之一，然而，肩袖肌腱的愈合是不可预测的，短期到中期的失败率在30- 94%之间。大多数肩袖疾病与肩袖组织的慢性退行性变有关。退行性改变可通过肌腱的磨损性改变和不可逆的肌腱套肌肉脂肪变性导致大量的、不可修复的肌腱套撕裂。迄今为止，大多数肌腱套实验研究都使用了急性损伤和修复动物模型（即健康肌肉和肌腱受伤后立即修复）。这些研究虽然有价值，但仅与临床上看到的一小部分肩袖病例相关。在这一建议中，我们试图使用我们新开发的、临床相关的肩袖疾病动物模型来检查肩袖变性和修复。了解肩袖退行性变的过程以及退行性袖带愈合的可能性将大大提高临床医生治疗肩袖疾病的能力。肌肉骨骼组织对其所处的机械环境高度敏感。临床和实验研究支持这样一种观点，即负荷减少，无论是通过肌腱损伤还是去神经支配，都会导致肌肉和肌腱变性。肩袖肌腱撕裂使肩袖肌肉脱落，使其容易恶化，最终形成慢性退化，无法修复的肩袖。对于肩袖修复，机械载荷的作用更为复杂。在急性肩袖修复中，保护性固定有利于愈合，但完全去除负荷不利于愈合。了解机械环境对肩袖退化和慢性退化袖带修复的作用将使我们能够提出康复策略，以最大限度地恢复肌肉并提高手术修复后的愈合。因此，本研究的总体目的是研究机械环境在肩袖退变和愈合中的作用。我们的方法将使用大鼠肩袖动物模型来研究肩袖退化（目的1）和修复（目的3和4）。我们将把动物模型的结果与临床数据进行比较，以验证我们的基础科学研究与人类状况相关（目标2）。

DESCRIPTION (provided by applicant): The rotator cuff muscles of the shoulder provide stability and motion at the glenohumeral joint. Rotator cuff disease is a degenerative condition that leads to significant shoulder pain, muscle atrophy, and tendon rupture, severely limiting upper extremity function. Rotator cuff repair to treat shoulder pain and restore strength is one of the most common orthopedic surgical procedures, however, rotator cuff tendon healing is unpredictable, with short to midterm failure rates ranging from 30- 94%. The majority of rotator cuff disease is related to chronic degeneration of the cuff tissues. Degenerative changes can lead to massive, irreparable rotator cuff tears through attritional changes in the tendons and irreversible fatty degeneration of the rotator cuff muscles. To date, most rotator cuff experimental studies have used acute injury and repair animal models (i.e., a healthy muscle and tendon is injured and then immediately repaired). These studies, while valuable, are only relevant to a small percentage of the rotator cuff cases seen clinically. In this proposal we seek to examine rotator cuff degeneration and repair using our newly developed, clinically relevant, animal model of rotator cuff disease. Understanding the process of rotator cuff degeneration and the potential for a degenerated cuff to heal will greatly enhance the clinician's ability to treat rotator cuff disease. Musculoskeletal tissues are highly sensitive to their mechanical environment. Clinical and experimental studies support the idea that decreased loading, either through tendon injury or denervation, leads to muscle and tendon degeneration. Rotator cuff tendon tears unload the rotator cuff muscles, leaving them vulnerable to deterioration and ultimately a chronically degenerated, irreparable rotator cuff. With regard to rotator cuff repair, the role of mechanical loading is more complex. In acute rotator cuff repairs, protective immobilization is beneficial to healing but complete removal of loading is detrimental to healing. Understanding the role of the mechanical environment for rotator cuff degeneration and repair of chronically degenerated cuffs will allow us to propose rehabilitation strategies to maximize muscle recovery and improve healing after surgical repair. Therefore, the overall objective in this study is to examine the role of the mechanical environment on rotator cuff degeneration and healing. Our approach will use a rat rotator cuff animal model to study cuff degeneration (Aim 1) and repair (Aims 3 and 4). We will compare results in our animal model to clinical data to validate that our basic science studies are relevant to the human condition (Aim 2). PUBLIC HEALTH RELEVANCE: The rotator cuff muscles of the shoulder provide stability and motion at the glenohumeral joint. Rotator cuff disease is a degenerative condition that leads to significant shoulder pain, muscle atrophy, and tendon rupture, severely limiting upper extremity function. Rotator cuff repair to treat shoulder pain and restore strength is one of the most common orthopedic surgical procedures, with over 75,000 repairs performed each year in the United States. However, rotator cuff tendon healing is unpredictable, with short to midterm failure rates ranging from 30- 94%.