The role of collagenolytic matrix metalloproteinases in the loss of articular cartilage in osteoarthritis.
Digestion of cartilage collagen is a critical step in the loss of articular cartilage in osteoarthritis (OA). The hypothesis that matrix metalloproteinases (MMPs) are the primary enzymes involved in cartilage collagen digestion is supported by evidence that indicates that: 1) one or more MMP can digest the extracellular matrix components in vitro, 2) the enzymes are expressed in OA cartilage at the place and time of cartilage destruction, 3) specific digestion products of MMP are present in the OA cartilage, and 4) experimental strategies that alter the expression and/or the activity of MMP alter the progression of cartilage destruction in OA. These observations suggest that MMPs in general and collagenolytic MMPs in particular are promising targets for treatment of OA.
Smith
Gerald N
GN
Division of Rheumatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202-5126, USA. gnsmith@iupui.edu
D002358:Cartilage, Articular / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000378:metabolism*; D010003:Osteoarthritis / Q000201:enzymology* / Q000503:physiopathology*
D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D003094:Collagen; D020782:Matrix Metalloproteinases