Inflammation and Knee Osteoarthritis

描述（由申请人提供）：症状性膝关节骨关节炎（OA）影响6%的美国成年人口和12 - 13%的60岁及以上人口。在老年人中，膝关节和髋关节OA是导致行动不便的最常见原因，也是导致功能性任务困难和依赖他人的主要原因。医疗往往不能充分缓解疼痛和残疾。长期以来，炎症一直被认为在加速OA进展和导致疼痛方面发挥作用。如果是这样，治疗可能会影响OA的长期病程和影响。全身炎症在OA中的作用是本项目的重点。虽然一些研究表明OA患者的全身炎症介质升高，但其他研究尚未发现相关性或表明存在此类关联，因为对本身与炎症相关的因素（如肥胖和年龄）调整不足。我们将重点关注全身性炎症及其介质的表型和基因型特征，以描述全身性炎症在OA发生和进展中的作用。我们将使用来自膝关节OA流行病学研究的数据，即多中心骨关节炎研究（MOST），该研究中大量受试者反复出现膝关节Mires，可以评估软骨丢失和滑膜增厚（关节内炎症部位）。我们将在一个亚组中进行钆对比增强MRI，以改善滑膜的可视化。我们认为，炎症可能与软骨损失不同，而不是关节疼痛。其目的是：评价全身炎症指标的横向和纵向关系（包括与增强的炎症反应相关的表型标志物，如CRP和遗传多态性）与MRI上膝关节软骨损失和膝关节疼痛：检查全身炎症的作用是否通过对关节内炎症的直接作用介导（滑膜增厚），导致全身炎症对疼痛或软骨损失的间接影响;并检查衰老对软骨损失的影响是否部分由随着年龄增长而发生的炎症标志物的升高来解释。大规模纵向研究、全身和局部炎症的测量以及膝关节OA特征的综合表征相结合，使得拟议的研究可能会对炎症与这种主要致残性疾病的关系产生独特的见解。

DESCRIPTION (provided by applicant): Symptomatic knee osteoarthritis (OA) affects 6% of the U.S. adult population and 12-13% of those ages 60 and over. In elders, OA of the knee and hip are the most common causes of mobility disability and are a leading cause of difficulty with functional tasks and of dependence on others. Medical treatment often fails to provide adequate relief of pain and disability. Inflammation has long been thought to play a role in accelerating progression and contributing to pain in OA. If so, treating it might affect the long term course and impact of OA. The role of systemic inflammation in OA is the focus of this project. While some studies have shown systemic inflammatory mediators are elevated in OA, others have not found a relationship or have suggested that such associations are present because of inadequate adjustment for factors that themselves are associated with inflammation, such as obesity and age. We shall focus on phenotypic and genotypic characterization of systemic inflammation and its mediators to characterize the role of systemic inflammation in the incidence and progression of OA. We will use data from an epidemiologic study of knee OA, the Multicenter Osteoarthritis Study (MOST), a study in which a large number of subjects have repeated knee Mires, permitting assessment of cartilage loss and synovial thickening, an intraarticular site of inflammation. We will perform gadolinium contrast enhanced MRIs in a subgroup to improve visualization of the synovium. We contend that inflammation may relate differently to cartilage loss than to joint pain. The aims are to: to evaluate the cross sectional and longitudinal relationship of systemic inflammation markers (including markers of phenotype such as CRP and genetic polymorphisms linked to enhanced inflammatory response) with cartilage loss in the knee on MRI and with knee pain: examine whether effects of systemic inflammation are mediated through direct effects on intraarticular inflammation (synovial thickening), leading to indirect effects of systemic inflammation on either pain or cartilage loss; and examine whether effects of aging on cartilage loss are explained, in part, by the rise in inflammatory markers that occurs with age. The combination of a large scale longitudinal study, measures of systemic and local inflammation and a comprehensive characterization of features of knee OA makes it likely that the proposed study will produce unique insights into the relation of inflammation with this major disabling disease.