Metalloproteinases: their role in arthritis and potential as therapeutic targets.
Irreversible degradation of articular cartilage is a major feature of the arthritides, and its prevention is a therapeutic goal which has been difficult to achieve. Enzymes from the matrix metalloproteinase and ADAMTS (a disintegrin, a metalloproteinase, and thrombospondin motif) families are key mediators of cartilage extracellular matrix destruction. Inhibition of metalloproteinase activity is therefore a conceptually attractive therapeutic strategy, although clinical efficacy has not yet been demonstrated. This review outlines the biology behind metalloproteinases as drug targets in the arthritides, and poses important questions for the future design of such therapies.
Clark
Ian M
IM
School of Biological Sciences, University of, East Anglia, Norwich, NR4 7TJ, UK. i.clark@uea.ac.uk
Parker
Andrew E
AE
D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D000072198:ADAM17 Protein; D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000201:enzymology; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000201:enzymology; D002358:Cartilage, Articular / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology*; D051379:Mice; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
D016326:Extracellular Matrix Proteins; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D000072198:ADAM17 Protein; D008911:Minocycline