Are cytokines involved in osteoarthritic pathophysiology?

Abstract

The putative role and mechanism of action of cytokines in the progression of arthritic diseases such as osteoarthritis (OA) has received particular attention because of the important interaction between articular cartilage and synovium in the pathophysiology of the diseased state. Maintaining matrix homeostasis in the normal adult cartilage phenotype requires normal turnover of matrix components, principally collagen and proteoglycan. Chondrocytes and synovial fibroblasts are targeted, via specific cell-surface receptors, by cytokines like interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) to produce matrix proteases and to suppress the synthesis of collagen and proteoglycan. Thus, cytokines not only favor tissue destruction, but also inhibit tissue repair. A structurally heterogeneous group of factors capable of directly antagonizing cytokine action is described, which acts either by blocking cytokine-receptor binding, inhibiting local cytokine synthesis, or complexing the cytokine into an inactive form. Furthermore, many growth factors, such as transforming growth factor-beta (TGF-beta), can counteract the net effect of cytokines by stimulating the synthesis of matrix components or natural inhibitors of cartilage degrading enzymes.