Rowan Andrew D, Young David A
Musculoskeletal Research Group, School of Clinical Medical Sciences, Catherine Cookson Building, Medical School, Framlington Place, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom.
Front Biosci. 2007 Jan 1;12:536-50. doi: 10.2741/2080.
The essentially irreversible degradation of articular cartilage collagen represents a key, rate-limiting process in arthritic diseases. This process is typically initiated as a consequence of an inflammatory response, and if left unchecked ultimately leads to loss of joint function, pain, disability and a need for joint replacement surgery. Although we have identified the enzymes capable of effecting such destructive proteolysis, and considerable evidence indicates that tumour necrosis factor alpha and interleukin-1 are major pro-inflammatory mediators in joint destruction, we still know relatively little about how these mediators regulate collagenase gene expression in chondrocytes. Inflammatory arthritis has long been considered to be synovium-driven but compelling data now also implicate the chondrocyte, the sole cell type present in cartilage, as an active player in the destructive process. An understanding of how different cytokines interact, and how the pathways they activate cross-talk will not only provide important new insight into the mechanisms of joint destruction but also identify new targets for therapeutic intervention.
关节软骨胶原蛋白的基本不可逆降解是关节炎疾病中的一个关键限速过程。这个过程通常由炎症反应引发，如果不加以控制，最终会导致关节功能丧失、疼痛、残疾以及需要进行关节置换手术。尽管我们已经确定了能够引发这种破坏性蛋白水解的酶，并且大量证据表明肿瘤坏死因子α和白细胞介素-1是关节破坏中的主要促炎介质，但我们对这些介质如何调节软骨细胞中胶原酶基因表达仍知之甚少。炎症性关节炎长期以来一直被认为是滑膜驱动的，但现在有令人信服的数据表明，软骨中唯一的细胞类型——软骨细胞也是破坏过程中的积极参与者。了解不同细胞因子如何相互作用，以及它们激活的途径如何相互影响，不仅将为关节破坏机制提供重要的新见解，还将确定治疗干预的新靶点。
