An Integrative Approach to Osteoarthritis and Obesity

描述（由申请人提供）：骨关节炎（OA）是一种使人衰弱和疼痛的关节疾病，影响约12%的25-74岁的美国总人口。肥胖人群的发病率甚至更高。本研究的目的是了解运动训练如何影响肥胖相关OA的发病机制。我们假设适度的运动训练可以减轻和延迟饮食诱导的肥胖小鼠OA的发病。为了验证这一点，我们将研究非肥胖久坐小鼠、肥胖久坐小鼠和肥胖运动小鼠。对于每一组，我们将确定：1)自愿笼子活动水平、首选速度和步态特征，以更好地了解影响关节负荷的因素；2)血清促炎细胞因子（如il、IL-17和tnf - α）、一氧化氮和前列腺素水平，以了解全身性炎症在OA发病中的作用；3)膝关节软骨的压缩和拉伸特性和组织学分级，以量化OA软骨退变的参数。这些研究将显著提高我们对骨性关节炎发病机制的理解，以及“生物力学”疗法（如减肥和运动）在减少疾病进展方面的疗效。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is a debilitating and painful joint disease affecting an estimated 12% of the total United States population between 25-74 years of age. The incedence is even greater among obese individuals. The goal of this study is to understand how exercise training affects the pathogenesis of obesity-linked OA. We hypothesize that moderate exercise training mitigates and delays the onset of OA in diet-induced obese mice. To test this, we will study non-obese sedentary, obese sedentary, and obese exercise-trained mice. For each group we will determine: 1) voluntary cage activity levels, preferred speeds, and gait characteristics to better understand the factors affecting joint loading, 2) serum levels of pro-inflammatory cytokines (e.g. ILl, IL-17, and TNF-alpha), nitric oxide, and prostaglandins to understand the role of systemic inflammation in the pathogenesis of OA, and 3) compressive and tensile properties and histological grades of knee joint cartilage to quantify the parameters of cartilage degeneration that characterize OA. These studies will significantly improve our understanding of different mechanisms involved in the pathogenesis of OA and the efficacy of "biomechanical" therapies such as weight-loss and exercise in decreasing disease progression.