Inflammation and Knee Osteoarthritis

描述(申请人提供)：症状性膝骨性关节炎(OA)影响6%的美国成年人和12%-13%的60岁及以上的人。在老年人中，膝关节和髋关节的骨性关节炎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。医疗治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骨性关节炎的进展和导致疼痛方面发挥了作用。如果是这样的话，治疗它可能会影响骨性关节炎的长期进程和影响。全身性炎症在骨性关节炎中的作用是本研究的重点。虽然一些研究表明，系统性炎症介质在骨性关节炎中升高，但另一些研究尚未发现两者之间存在联系，或表明存在这种联系是因为对肥胖和年龄等本身与炎症相关的因素调整不足。我们将重点研究全身炎症及其介体的表型和基因特征，以确定全身炎症在骨性关节炎的发生和发展中的作用。我们将使用膝骨性关节炎的流行病学研究数据，即多中心骨关节炎研究(MOST)，在该研究中，大量受试者重复膝关节损伤，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Gd增强磁共振成像，以改善滑膜的可视化。我们认为，炎症与软骨丢失的关系可能与关节疼痛不同。其目的是：评估全身炎症标记物(包括与增强的炎症反应有关的表型标记物和基因多态性)与膝关节MRI上的软骨丢失和膝关节疼痛的横断面和纵向关系：检查全身炎症的影响是否通过对关节内炎症(滑膜增厚)的直接影响而介导，从而导致全身炎症对疼痛或软骨丢失的间接影响；以及检查是否部分地通过随年龄增加的炎症标记物的升高来解释软骨丢失的影响。一项大规模的纵向研究、全身和局部炎症的测量以及对膝骨性关节炎特征的全面描述相结合，使拟议的研究有可能对炎症与这一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.