NSAIDs and human cartilage metabolism

Abstract

It is now generally accepted that the extracellular matrix of human articular cartilage is in a state of dynamic equilibrium. The synthesis of both proteoglycan and collagen by the chondrocytes and the natural turnover of these molecules by enzymes released from these cells maintains a balance which is essential for the structural integration and function of the extracellular macromolecules. Under pathological conditions this balance may be disturbed by changes in the anabolic or catabolic activity of the indigenous chondrocytes or by the actions of surrounding connective tissues [1]. Thus, in rheumatoid arthritis (RA), where pannus erosion of cartilage is one of the prime causes of articular damage, it is lik:ely that the extrinsic proteases, and in particular, metalloproteinases, of the synovial fibroblasts and inflammatory cells are responsible for much of the erosive process. This effect is probably compounded by the action of cytokines on the cartilage chondrocytes inhibiting proteoglycan (GAG) synthesis and hence diminishing repair processes. This effect of cytokines in inhibiting synthesis is now well documented but has still not received the attention that it probably warrants. Studies by Dingle et al. [2] have demonstrated that human cartilage is extremely sensitive to inhibition of GAG synthesis — <0.01 ng ml^-1 h^-1 IL1a will give >50% inhibition of chondrocytic matrix synthesis in normal, osteoarthritic (OA) and RA cartilage, the most severe effects being seen in those tissues with high metabolic activity.