Rotator Cuff Degeneration and Repair

描述（由申请人提供）：肩关节的肩袖肌肉为盂肱关节提供稳定性和运动。肩袖疾病是一种退行性疾病，可导致严重的肩痛、肌肉萎缩和肌腱断裂，严重限制上肢功能。肩袖修复治疗肩关节疼痛和恢复力量是最常见的骨科手术之一，然而，肩袖肌腱愈合是不可预测的，短期至中期失败率为30- 94%。大多数肩袖疾病与肩袖组织的慢性变性有关。退行性变化可通过肌腱的磨损变化和肩袖肌肉的不可逆脂肪变性导致巨大的、不可修复的肩袖撕裂。迄今为止，大多数肩袖实验研究使用急性损伤和修复动物模型（即，一个健康的肌肉和肌腱受伤，然后立即修复）。这些研究虽然有价值，但仅与临床上观察到的一小部分肩袖病例相关。在这个建议中，我们试图检查肩袖退化和修复使用我们新开发的，临床相关的，肩袖疾病的动物模型。了解肩袖退变的过程和退变的肩袖愈合的可能性将大大提高临床医生治疗肩袖疾病的能力。肌肉骨骼组织对其力学环境高度敏感。临床和实验研究支持这样一种观点，即通过肌腱损伤或去神经支配减少负荷会导致肌肉和肌腱退化。肩袖肌腱撕裂使肩袖肌肉卸载，使它们容易退化，最终形成慢性退化、不可修复的肩袖。对于肩袖修复，机械负荷的作用更为复杂。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。了解肩袖退变和修复慢性退变袖的力学环境的作用，将使我们能够提出康复策略，以最大限度地恢复肌肉，并改善手术修复后的愈合。因此，本研究的总体目标是检查力学环境对肩袖退变和愈合的作用。我们的方法将使用大鼠肩袖动物模型来研究肩袖退化（目标1）和修复（目标3和4）。我们将比较动物模型的结果与临床数据，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).