Rotator Cuff Degeneration and Repair

肩袖退化和修复

• 批准号: 8698275
• 负责人: Leesa M Galatz
• 金额: $ 25.74万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-15 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698275
• 关键词: Accounting; Acute; Algorithms; Animal Model; Animals; Atrophic; Basic Science; Biological; Biomechanics; Chemicals; Chronic; Clinical Data; Clinical Research; Complex; Data; Degenerative Disorder; Denervation; Deterioration; Development; Differentiation and Growth; Disease; Drug usage; Electromyography; Ensure; Environment; Excision; Failure; Fatty acid glycerol esters; Future; Genes; Genetic Markers; Goals; Healed; Human; Immobilization; Injury; Intervention; Intramuscular; Joints; Knock-out; Knockout Mice; Lead; Left; Mechanics; Modeling; Motion; Mus; Muscle; Muscle function; Muscular Atrophy; Musculoskeletal; Operative Surgical Procedures; Orthopedic Surgical Procedures; Pathology; Patients; Procedures; Process; Property; Protocols documentation; Rattus; Recovery; Rehabilitation therapy; Rodent; Role; Rotator Cuff; Rupture; Shoulder; Shoulder Pain; Staging; Suramin; Tendon Injuries; Tendon structure; Time; Tissues; United States; Upper Extremity; clinically relevant; healing; improved; in vivo; injured; injury and repair; lipid biosynthesis; muscle degeneration; muscle form; muscle regeneration; myogenesis; myostatin; new therapeutic target; outcome forecast; prevent; rehabilitation strategy; repaired; research study; treatment strategy

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).

描述(申请人提供)：肩袖的肩袖肌肉在肩关节处提供稳定和运动。肩袖疾病是一种退行性疾病，会导致严重的肩痛、肌肉萎缩和肌腱断裂，严重限制上肢功能。肩袖修复治疗肩部疼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，短期到中期失败率从30%到94%不等。大多数肩袖疾病与肩袖组织的慢性变性有关。退行性改变可通过肌腱的磨损性改变和肩袖肌肉的不可逆转的脂肪变性而导致大量的、无法修复的肩袖撕裂。到目前为止，大多数肩袖实验研究都采用了急性损伤和修复的动物模型(即健康的肌肉和肌腱受伤后立即修复)。这些研究虽然有价值，但只与临床上看到的一小部分肩袖病例有关。在这项建议中，我们试图使用我们新开发的具有临床相关性的肩袖疾病动物模型来检查肩袖退变和修复。了解肩袖退变的过程和退变袖带愈合的可能性将极大地提高临床医生治疗肩袖疾病的能力。肌肉骨骼组织对其机械环境高度敏感。临床和实验研究支持这一观点，即减少负荷，无论是通过肌腱损伤或失神经，导致肌肉和肌腱退化。肩袖肌腱撕裂使肩袖肌肉不堪重负，使其容易恶化，最终导致肩袖长期退化，无法修复。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，但完全解除负荷不利于愈合。了解机械环境在肩袖退行性变和慢性退行性袖带修复中的作用，将使我们能够提出康复策略，以最大限度地促进肌肉恢复，并改善手术修复后的愈合。因此，本研究的总体目标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袖带退变(目标1)和修复(目标3和4)。我们将把我们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)。