In Vivo Rabbit Model of Finger Muscoloskeletal Disorders

手指肌肉骨骼疾病的体内兔模型

• 批准号: 6682425
• 负责人: KAREN B KING
• 金额: $ 27.73万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6682425
• 关键词: biomechanics; bone; cartilage; disease /disorder model; electrostimulus; fingers; gene expression; in situ hybridization; joints; laboratory rabbit; ligaments; morphology; musculoskeletal disorder; occupational disease /disorder; occupational stressor; osteoarthritis; polymerase chain reaction; protein localization; protein structure function; repetitive motion injury; western blottings

DESCRIPTION (provided by applicant): The ongoing rise in costs and morbidity associated with occupational musculoskeletal disorders (MSDs) demands the investigation of known risk factors for injury. Repetition of movement, forceful loading and their combination (repetitive loading) are risk factors for MSDs. These happen to be some of the few modifiable risk factors for MSDs of the hand and other joints. This project proposes to use an in vivo animal model of repetitive finger joint loading to elucidate the relative risks of these factors (repetition and combined force and repetition). Finger joint loading is used to simulate hand intensive tasks found in the workplace to test the following hypothesis: The combination of force and repetition is an occupational risk factor for MSD. This project will quantify the structural and molecular changes in joint tissues due to repetitive loading. And finally, this project will determine the threshold of repetitive loading in a dose-response study. The long term goals of this study are to 1) determine the relative contributions of individual biomechanical characteristics of finger joint loading, namely repetition, force level, and duration of exposure; and 2) demonstrate causality between these biomechanical risk factors, cellular response, tissue damage, and injury. The results of this mechanobiology project will lead to guidelines for effective interventions of MSDs of the hand joints such as osteoarthritis (OA) or degenerative joint disease (DJD). This project directly addresses the National Occupational Research Agenda (NORA) in 1) developing a quantitative dose-response model identifying dose-response relationships, 2) determining whether the injury response of the tissue has more to do with repetition of loading or level of peak load, and 3) identifying the ultrastructural injury and biochemical alterations associated with physical loading.

描述（由申请人提供）：与职业性肌肉骨骼疾病（MSDs）相关的成本和发病率的持续上升要求对已知的伤害风险因素进行调查。重复运动、强力负荷及其组合（重复负荷）是MSDs的危险因素。这些恰好是手部和其他关节的MSDs的少数可改变的风险因素。本项目拟采用重复性手指关节负荷的体内动物模型来阐明这些因素（重复及联合力和重复）的相对风险。手指关节负荷被用来模拟在工作场所发现的手部密集任务，以验证以下假设：力和重复的组合是MSD的职业风险因素。该项目将量化关节组织在重复载荷下的结构和分子变化。最后，本项目将确定剂量-反应研究中重复负荷的阈值。本研究的长期目标是：1)确定手指关节载荷的个体生物力学特征的相对贡献，即重复、力水平和暴露时间；2)证明这些生物力学风险因素、细胞反应、组织损伤和损伤之间的因果关系。该机械生物学项目的结果将为有效干预手关节的MSDs（如骨关节炎（OA）或退行性关节疾病（DJD））提供指导。该项目直接解决了美国国家职业研究议程（NORA）的问题：1)建立定量剂量-反应模型，确定剂量-反应关系；2)确定组织的损伤反应是否与重复负荷或峰值负荷水平有关；3)确定与物理负荷相关的超微结构损伤和生化改变。