Cartilage catabolism in arthritis: factors that influence homeostasis

Abstract

Preventing the destruction of articular cartilage has long been a goal in the treatment of arthritic diseases, in which a combination of cytokines and growth factors affect the catabolic state of cells within the joint. Normal tissue turnover can be viewed as a balance between degradation and synthesis of the macromolecules that constitute the extracellular matrix. This process is tightly regulated such that highly degradative proteinases are controlled at several levels, including synthesis and secretion, activation and inhibition. Tissue destruction occurs when proteinase-mediated degradation exceeds synthesis, and this is markedly influenced by cytokines and growth factors that stimulate matrix synthesis as well as the production of proteinases and/or their endogenous inhibitors. This review outlines current knowledge of factors that influence cartilage biology, with particular emphasis on chondrocytes and synovial fibroblasts. Recent findings from the delivery of cytokines to affected tissues are also summarised, and the potential impact these observations might have on new therapies for arthritic diseases is discussed.