Strength Training and Arthritis Trial

描述(由申请人提供)：股四头肌肌肉力量丧失直接导致膝关节骨关节炎(OA)相关的疼痛、残疾和发病率。UP的强度损失 到40%通常发生在膝骨性关节炎的发生和发展之前。有趣的证据表明，与骨性关节炎相关的股四头肌无力可能是肌肉质量改变的结果，而且肌肉无力实际上可能先于骨性关节炎的发展。我们假设，肌肉环境的变化，包括炎症细胞渗透、纤维化、脂肪渗透和干细胞活动的变化，都会导致与骨性关节炎相关的肌肉无力。验证这一假说是父母资助的自然延伸，该资助寻求评估加强计划对股四头肌力量、疼痛、残疾和关节负荷的影响。BIRT应用程序将首次将该领域的专家聚集在一起 对肌肉生物学和关节生物学/生物力学的研究，以评估肌肉内部的适应性，这可能导致膝盖骨关节炎患者的力量丧失。来自健康对照组和膝骨性关节炎患者股外侧肌的肌肉活检将被评估肌肉纤维的形态、大小和类型，以及免疫细胞渗透的标志。肌肉干细胞(卫星细胞)的丰度和其他祖细胞种群的丰度将被量化，以确定可能限制肌肉适应性的变化。这些特性将与肌肉的力量测量和横截面积进行比较，以确定它们之间的关系。我们提出了两个特定的目标：在目标1中，我们假设膝关节骨关节炎与股四头肌中的中性粒细胞和炎性巨噬细胞的渗透有关。在目标2中，我们假设膝骨性关节炎与肌肉祖细胞种群的改变有关，导致脂肪堆积和纤维化，以肌肉修复、维持和生长为代价。为了实现这些目标，BIRT应用程序将维克森林大学父母资助的梅西尔和勒泽博士与肯塔基大学的彼得森和诺伦博士聚集在一起。我们建议从父母赠款的基线上从患者身上提取20例肌肉活检，并将它们与年龄、性别、种族、活动和体重指数匹配的健康对照受试者进行比较，这些受试者没有膝骨性关节炎的放射学或症状史。免疫组织化学分析将确定肌肉环境的特征。这些数据将极大地加快研究小组对运动响应者和非响应者的特征进行评估，针对已确定的适应情况制定最佳运动处方，并确定那些在疾病过程早期可能最有可能面临力量丧失风险的人。

DESCRIPTION (provided by applicant): Quadriceps muscle strength loss contributes directly to the pain, disability and morbidity associated with knee osteoarthritis (OA). Strength loss of up to 40% typically occurs and may actually precede the development of knee OA. Intriguing evidence suggests that OA-associated quadriceps weakness may be the result of altered muscle quality, and that muscle weakness may actually precede the development of OA. We hypothesize that changes in the muscle environment, including inflammatory cell infiltration, fibrosis, fat infiltration, and changes in stem cell activity contribute to muscle weakness associated with OA. Testing this hypothesis is a natural extension of the parent grant which seeks to assess the effect of strengthening programs on quadriceps strength, pain, disability, and joint loading. The BIRT application will bring together for the first time experts in the areas of muscle biology and joint biology/biomechanics to assess the adaptations within muscle that may contribute to the strength loss seen in those suffering with knee OA. Muscle biopsies from the vastus lateralis of control healthy subjects and patients with knee OA will be assessed for muscle fiber morphology, size and type, as well as markers of immune cell infiltration. Muscle stem cell (satellite cell) abundance and the abundance of other progenitor populations will be quantified to identify changes that may limit muscle adaptability. These properties will be compared to the strength measures and cross sectional area of the muscle to determine their relationship. We propose two specific aims: in Aim 1 we hypothesize that knee OA is associated with neutrophil and pro-inflammatory macrophage infiltration in the quadriceps muscle. In Aim 2 we hypothesize that knee OA is associated with alterations in muscle progenitor populations resulting in fat accumulation and fibrosis, at the expense of muscle repair, maintenance, and growth. To accomplish these aims this BIRT application brings together Drs. Messier and Loeser from the parent grant at Wake Forest University with Drs. Peterson and Noehren at the University of Kentucky. We propose to take 20 muscle biopsies from patients at baseline from the parent grant and compare them to age-, sex-, race-, activity-, and BMI-matched healthy control subjects who have no radiographic or symptomatic history of knee OA. Immunohistochemcial analyses will characterize the muscle environment. These data will greatly accelerate the development of subsequent grants among the research team assessing characteristics of responders and non-responders to exercise, optimal exercise prescription to target the identified adaptations, and identify those early in the disease process who might be most at risk for strength loss.