Strength Training and Arthritis Trial

力量训练和关节炎试验

• 批准号: 8583156
• 负责人: Stephen P Messier
• 金额: $ 13.77万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8583156
• 关键词: Address; Adult; Age; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Area; Arthritis; Biology; Biomechanics; Biopsy; Cell Survival; Cells; Characteristics; Collaborations; Cryoultramicrotomy; Data; Degenerative polyarthritis; Development; Disease; Environment; Exercise; Fatty acid glycerol esters; Fibrosis; Freezing; Future; Grant; Growth; Harvest; Health; Immunologic Markers; Individual; Infiltration; Inflammatory; Intervention; Investigation; Isotonic Exercise; Joints; Kentucky; Knee Osteoarthritis; Knee joint; Location; Maintenance; Measures; Morbidity - disease rate; Morphology; Muscle; Muscle Fibers; Muscle Weakness; Muscle satellite cell; Natural regeneration; Outcome; PDGFRB gene; Pain; Participant; Patients; Population; Prevalence; Process; Property; Race; Recording of previous events; Recruitment Activity; Regimen; Relative (related person); Research; Risk; Source; Stem cells; Symptoms; Testing; Time; Universities; clinically significant; disability; disabling disease; forest; improved; joint loading; macrophage; muscle strength; neutrophil; novel therapeutic intervention; parent grant; progenitor; programs; public health relevance; quadriceps muscle; rehabilitation strategy; repaired; response; satellite cell; sex; strength training; vastus lateralis

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.

描述（由申请人提供）：股四头肌强度损失直接导致膝盖骨关节炎（OA）相关的疼痛，残疾和发病率。强度损失 通常发生到40％，实际上可能是在膝盖OA的发展之前。有趣的证据表明，与OA相关的股四头肌无力可能是肌肉质量改变的结果，而肌肉无力实际上可能在OA的发展之前。我们假设肌肉环境的变化，包括炎性细胞浸润，纤维化，脂肪浸润以及干细胞活性的变化有助于与OA相关的肌肉无力。检验该假设是父母赠款的自然扩展，该赠款旨在评估加强程序对股四头肌强度，疼痛，残疾和关节载荷的影响。 BIRT申请将首次在该地区的专家组合在一起 肌肉生物学和联合生物学/生物力学评估肌肉中的适应性，这可能导致患有膝盖OA患者的力量损失。将评估来自对照健康受试者和膝盖OA患者的大量外侧的肌肉活检，以评估肌肉纤维形态，大小和类型以及免疫细胞浸润的标志物。将量化肌肉干细胞（卫星细胞）丰度和其他祖细胞种群的丰度，以识别可能限制肌肉适应能力的变化。这些特性将与肌肉的强度度量和横截面区域进行比较，以确定其关系。我们提出了两个具体的目标：在目标1中，我们假设膝盖OA与股四头肌肌肉中的嗜中性粒细胞和促炎性巨噬细胞浸润有关。在AIM 2中，我们假设膝盖OA与肌肉祖细胞种群的改变有关，导致脂肪积累和纤维化，牺牲肌肉修复，维护和生长。为了实现这些目标，该Birt应用程序将Drs汇集在一起​​。 Wake Forest University的父母Grant的Messier和Loeser和Drs。肯塔基大学的彼得森和诺伦。我们建议从基线的患者手段从父母赠款中获得20次肌肉活检，并将其与没有膝关节OA的放射线学或有症状病史的年龄，性别，种族，活动，活动 - 和BMI匹配的健康对照受试者进行比较。免疫组织化学分析将表征肌肉环境。这些数据将极大地加速研究小组之间随后的赠款的发展，以评估响应者的特征和非反应者进行运动，最佳的运动处方，以针对已确定的适应，并确定可能在疾病过程的早期，他们可能最有可能造成力量损失的风险。