The development of cartilage pathology in osteoarthritis involves excessive damage to the collagen fibrillar network, which appears to be mediated primarily by the chondrocyte-generated cytokines interleukin-1 and tumour necrosis factor α and the collagenases matrix metalloproteinase-1 (MMP-1) and MMP-13. The damage to matrix caused by these and other MMPs can result in the production of sufficient degradation products that can themselves elicit further degradation, leading to chondrocyte differentiation and eventually matrix mineralization and cell death. Knowledge of these MMPs, cellular receptors and cytokine pathways, and the ability to selectively antagonize them by selective blockade of function, may provide valuable therapeutic opportunities in the treatment of osteoarthritis and other joint diseases involving cartilage resorption, such as rheumatoid arthritis. The ability to detect the products of these degradative events released into body fluids of patients may enable us to monitor disease activity, predict disease progression and determine more rapidly the efficacy of new therapeutic agents.
Proteolysis of the collagen fibril in osteoarthritis
- Views Icon Views
- Share Icon Share
Jeremy Saklatvala, Hideaki Nagase, Guy Salvesen, A Robin Poole, Fred Nelson, Leif Dahlberg, Elena Tchetina, Masahiko Kobayashi, Tadashi Yasuda, Sheila Laverty, Ginette Squires, Toshihisa Kojima, William Wu, R. Clark Billinghurst; Proteolysis of the collagen fibril in osteoarthritis. Biochem Soc Symp 1 September 2003; 70 115–123. doi: https://doi.org/10.1042/bss0700115
Download citation file: