Inflammation and Knee Osteoarthritis

炎症和膝骨关节炎

• 批准号: 7123717
• 负责人: Cora E Lewis
• 金额: $ 26.4万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123717
• 关键词: aging; cartilage; clinical research; epidemiology; genetic polymorphism; genetic susceptibility; genotype; human middle age (35-64); human old age (65+); human subject; immune response; immunogenetics; inflammation; information systems; knee; linkage disequilibriums; longitudinal human study; magnetic resonance imaging; musculoskeletal imaging /visualization /scanning; osteoarthritis; pain; phenotype; synovial membrane

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.

描述（由申请人提供）：有症状的膝关节骨关节炎（OA）影响了6％的美国成年人口，而60岁及以上的年龄占12-13％。在长者中，膝盖和髋关节的OA是造成流动性残疾的最常见原因，是功能任务和依赖他人的困难的主要原因。医疗通常无法充分缓解疼痛和残疾。长期以来，人们一直认为炎症在加速进展并导致OA疼痛方面发挥作用。如果是这样，治疗可能会影响OA的长期过程和影响。系统性炎症在OA中的作用是该项目的重点。尽管一些研究表明，OA的全身性炎症介质升高，但其他研究却没有发现关系或建议，由于对自己与炎症（例如肥胖和年龄）的因素的调整不足，因此存在这种关联。我们将重点介绍系统性炎症及其介体的表型和基因型表征，以表征系统性炎症在OA发病率和进展中的作用。我们将使用膝关节OA的流行病学研究（多中心骨关节炎研究）（大多数）的数据，该研究是一项研究，其中大量受试者重复膝盖米尔斯，允许评估软骨损失和滑膜增厚，这是一种炎症内炎症的部位。我们将在亚组中执行Gadolinium对比增强的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，而与关节疼痛有关。目的是：评估系统性炎症标记物的横截面和纵向关系（包括表型的标记，例如CRP和与炎症反应增强的遗传多态性相关的表型标记）以及膝盖上MRI的软骨损失以及膝盖疼痛的软骨丧失以及与膝关节疼痛的软骨丧失：检查是否直接介导了对系统性炎症的影响（是否对全身炎症的影响）（是否对全身炎症产生）（是否对全体炎症产生）（是否是厚度的），是厚度的危险（是否是厚实的），该效应（是否是在内部炎症的影响）疼痛或软骨损失的炎症；并检查衰老对软骨损失的影响是否通过随着年龄的增长而发生的炎症标记的增加来解释。大规模纵向研究，全身性和局部炎症的度量以及膝盖OA特征的全面表征的结合使得拟议的研究可能会产生独特的见解，以了解炎症与这种主要残疾疾病的关系。