Proteolysis of the collagen fibril in osteoarthritis.
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 alpha 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.
Joint Diseases Laboratory, Shriners Hospitals for Children, Departments of Surgery and Medicine, McGill University, 1529 Cedar Avenue, Montreal, Quebec H3G IA6, Canada. rpoole@shriners.mcgill.ca
A Robin
AR
Poole
Fred
F
Nelson
Leif
L
Dahlberg
Elena
E
Tchetina
Masahiko
M
Kobayashi
Tadashi
T
Yasuda
Sheila
S
Laverty
Ginette
G
Squires
Toshihisa
T
Kojima
William
W
Wu
R Clark
RC
Billinghurst
D000375:Aging / Q000378:metabolism; D002358:Cartilage, Articular / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism*
D003094:Collagen; D020782:Matrix Metalloproteinases