[Destruction of articular cartilage]

Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF alpha), have been implicated in the dysregulation of bone and cartilage remodelling characteristic of rheumatoid arthritis (RA) and/or osteoarthritis (OA). These cytokines increase production of factors that stimulate cartilage matrix degradation such as metalloproteinases. The matrix metalloproteinases (MMPs), the a disintegrin and metalloproteinase (ADAMs) and a disintegrin and metalloproteinase with thrombospondin repeats (ADAM-TSs) are secreted by many cell types including chondrocytes and cells in the synovium under the influences of cytokines. The role of the matalloproteinases in the irreversible degradation of articular cartilage has been extensively documented. We have already succeeded in halting the progression of joint damage by RA using anti-TNF therapy. The precise understanding of the roles of metalloproteinases should provide new therapeutic strategies for OA.