The adaptive response of skeletal muscle, bone, and cartilage to severe knee trauma involving ACL disruption with and without concomitant injury to the meniscus

项目总结： 创伤后骨关节炎(PTOA)起病早，易发于年轻人， 活跃的个人以及需要更早的手术和康复干预，所有这些都会降低质量 生活的一部分。更广泛地说，12%的骨关节炎病例是由于关节创伤(1270万人)，每年花费30亿美元。 前十字韧带(ACL)和半月板的损伤是最常见的担忧 患膝部PTOA风险增加的个体。然而，在治疗中存在一个两难境地。 因为我们不了解创伤的严重程度如何影响PTOA的适应性反应 四肢(肌肉、骨骼和关节软骨)，以及伴随的半月板如何改变这些适应性 受伤、受试者的性别、体重指数和关节几何形状。此外，目前尚不清楚这些适应性反应是如何 与PTOA疾病进程的早期标志物的变化有关。这些知识差距代表了 开发更有效的、早期的PTOA治疗范例的关键障碍 了解骨骼肌、骨骼和关节软骨的适应性。到目前为止，还没有研究表明 在前交叉韧带损伤前对受试者进行前瞻性表征，然后评估肢体的适应性反应 到前交叉韧带断裂和手术重建。我们目前的知识库完全建立在回顾的基础上 研究，因此我们提出了一项前瞻性研究，将评估两个目标。 目的1：描述骨骼肌大小和功能、骨结构和骨骼的适应性变化。 严重膝关节创伤时产生的关节软骨基质成分；并确定如何 这些变化根据创伤类型的不同而有所不同(前交叉韧带断裂伴和不伴损伤 半月板)、患者的性别、体重指数和关节几何形状。 目的2：评价严重膝关节创伤对早期关节软骨厚度变化的影响。 PTOA的标志)，并确定这些影响是否被创伤中涉及的结构(前交叉韧带)改变 半月板断裂合并或不合并半月板损伤)、患者的性别、体重指数和关节几何形状； 由骨骼肌大小和功能、骨结构和关节软骨的适应性变化所调节 矩阵组件。 这项研究将提供受伤肢体多个组织对膝关节的综合适应性反应的数据 创伤和手术，从逻辑上讲建立在父母调查的基础上。这项研究将提供一种机械的 了解导致PTOA的膝关节病理演变，以及性别的调节作用， BMI和关节几何体。这项研究的知识将解决PTOA治疗进展的关键障碍 通过确定创伤的严重程度如何影响软骨结构，在干预措施将被 有效预防PTOA的发生或恶化：集中治疗PTOA的试验的障碍。

Project Summary: Post-traumatic osteoarthritis (PTOA) is debilitating due to its early onset, predisposition to affect younger, active individuals and the need for earlier surgical and rehabilitative interventions, all of which decrease quality of life. More broadly, 12% of OA cases are due to joint trauma (12.7 million people), costing $3 billion/yr. Injuries of the anterior cruciate ligament (ACL) and meniscus are the most common concerns that place individuals at increased risk of developing PTOA about the knee. However, a dilemma exists in the treatment of PTOA because we do not understand how the severity of the injury affects the adaptive responses of the limb (muscle, bone, and articular cartilage), nor how these adaptations are modified by concomitant meniscus injury, the subject's sex, BMI and joint geometry. Moreover, it is unknown how these adaptive responses are associated with changes in early markers of the PTOA disease process. These knowledge gaps represent critical barriers to developing more effective, early PTOA treatment paradigms that are informed by an understanding of adaptions in skeletal muscle, bone and articular cartilage. To date, no study has prospectively characterized subjects prior to ACL injury and then evaluated the adaptive response of the limb to ACL rupture and surgical reconstruction. Our current knowledge base is built entirely on retrospective studies, and consequently we propose a prospective study that will evaluate two aims. Aim 1: Characterize the adaptive changes in skeletal muscle size and function, bone architecture, and articular cartilage matrix components that occur in response to severe knee trauma; and determine how these changes differ depending on the type of trauma (ACL disruption with and without concomitant injury to the menisci), the patient's sex, BMI, and joint geometry. Aim 2: Assess the effects of severe knee trauma on change in thickness of the articular cartilage (an early marker of PTOA) and determine if these effects are modified by structures involved in the trauma (ACL disruption with and without concomitant meniscus injury), the patient's sex, BMI, and joint geometry; and mediated by adaptive changes in skeletal muscle size and function, bone architecture, and articular cartilage matrix components. The study will provide data on the integrative, adaptive response of multiple tissues of the injured limb to knee trauma and surgery and builds logically upon the parent investigation. The study will provide a mechanistic understanding of the evolution of knee joint pathology that leads to PTOA, and the modifying effects of sex, BMI and joint geometry. Knowledge from this study will address critical barriers to progress in PTOA treatment by determining how the severity of the trauma affects cartilage structure at a time when interventions will be effective for prevention of incident or worsening PTOA: the barrier to trials focused on treatment of PTOA.