The Pathophysiology of Rotator Cuff Tendon Injury and Healing in the Presence of

描述(申请人提供)：肩袖肌腱撕裂是一个广泛存在的骨科问题，通常需要手术修复以消除疼痛和恢复功能。手术修复的成功与否好坏参半，很大一部分患者因愈合失败和其他并发症(如关节僵硬)而再次撕裂。II型糖尿病是一种在过去十年中大幅增加的疾病，与组织特性改变、愈合不良和关节僵硬有关，这些都是肩袖修复患者的特征。不幸的是，研究糖尿病如何影响复杂的肌腱愈合反应和关节力学的研究有限。最近在I型糖尿病大鼠模型中的一项研究确定，在肩袖肌腱修复后，肌腱在愈合的早期阶段有相当大的力学性能缺陷。虽然这项研究强调了在存在高血糖的情况下肌腱愈合可能发生的机械变化，但它没有解决组织特性、生物机制和发生的关节运动受限的改变，也没有解决最常见的糖尿病形式。使用我们实验室成熟的在体冈上肌腱撕裂大鼠模型和广泛使用的Goto-Kakizaki大鼠作为II型糖尿病模型，可以直接检查在这种疾病状态下导致组织特性改变和肌腱愈合减少的机制，否则无法在人类身上进行研究。结合这两个公认的动物模型，本研究的总体目标是确定导致II型糖尿病引起的未损伤肌腱属性改变和不利肌腱愈合的机制。我们的全球假设是，II型糖尿病将导致生物介质的增加和延长，这将扰乱肌腱正常的未损伤属性和肌腱愈合的进程。我们的具体目标是：特定目标1：比较健康和II型糖尿病大鼠的肩关节力学和肌腱特性(力学、基因表达、蛋白质含量)；以及特定目标2：确定II型糖尿病对急性肩袖撕裂后肩关节力学和肩袖肌腱愈合(力学、基因表达和蛋白质含量)的影响。这些分析将深入了解受II型糖尿病影响的肩袖肌腱动态平衡和损伤修复反应的复杂过程，以及它们与功能限制的关系。这项研究的结果将为未来的研究提供框架，这些研究将试图从治疗上增强II型糖尿病中看到的有害生物介质的级联反应。最终，这将为医生提供更多有效治疗肌腱损伤的II型糖尿病患者的工具。 公共卫生相关性：这项研究将为糖尿病患者肩袖肌腱愈合延迟的潜在机制提供关键信息。然后，医生可以利用这些信息来为这些患者制定最佳治疗策略。

DESCRIPTION (provided by applicant): Rotator cuff tendon tears are a widespread orthopedic problem that often requires surgical repair to eliminate pain and restore function. The success of the surgical repair has been mixed, with a large percentage of patients suffering from re-tears due to failed healing and other complications, such as joint stiffness. Type II diabetes mellitus is one condition that has substantially increased over the past decade and is linked with altered tissue properties, poor healing and joint stiffness, which are hallmark characteristics of rotator cuff repair patients. Unfortunately, limited research exists examining how diabetes affects the complex tendon healing response and the mechanics of the joint. One recent study in a type I diabetic rat model determined that following rotator cuff tendon repair there are considerable deficits in tendon mechanical properties during the early stages of healing. Although this study highlighted the mechanical changes that could occur specifically with tendon healing in the presence of hyperglycemia, it does not address the altered tissue properties, biologic mechanisms, and the restricted joint motion that occur, nor did it address the most common form of diabetes. The use of our laboratory's well established in vivo rat model of supraspinatus tendon tears and the extensively used Goto-Kakizaki rat as a model for type II diabetes allows for the direct examination of the mechanisms that cause altered tissue properties and decreased tendon healing in this disease state, which would otherwise be impossible to study in the human. With the combination of these two well established animal models, the overall objectives of this study are to determine the mechanisms that lead to alterations in uninjured tendon properties and detrimental tendon healing caused by type II diabetes. Our global hypothesis is that type II diabetes will cause increased and prolonged biological mediators that will disrupt the normal uninjured properties of the tendon and progression of tendon healing. Our specific aims are: Specific Aim 1: To compare shoulder joint mechanics and tendon properties (mechanics, gene expression, protein content) of healthy and type II diabetic rats; and Specific Aim 2: To determine the effect of type II diabetes on shoulder joint mechanics and rotator cuff tendon healing (mechanics, gene expression, and protein content) following an acute rotator cuff tear. These analyses will provide insight into the complex processes of rotator cuff tendon homeostasis and repair response to injury that are affected by type II diabetes and how they relate to functional limitations. The results of this study will provide the framework for future studies that will attempt to therapeutically augment the deleterious cascade of biologic mediators seen in type II diabetes. Ultimately, this will provide physicians with further tools for efficiently treating patients with type II diabetes that are suffering from tendon injuries. PUBLIC HEALTH RELEVANCE: This study will provide crucial information into the underlying mechanisms that lead to delayed rotator cuff tendon healing in diabetic patients. This information can then be used by physicians to develop optimal treatment strategies for these patients.