Novel inhibitors of matrix metalloproteinase gene expression as potential therapies for arthritis.

Abstract

Matrix metalloproteinases are a family of endopeptidases that collectively degrade all components of the extracellular matrix at neutral pH. During the progression of arthritis, MMPs mediate the degradation of cartilage, which consists largely of Type II collagen fibrils and proteoglycans. The collagenases, a subgroup of MMPs, have the singular ability to cleave intact collagens and may provide a rate-limiting step in cartilage destruction. In arthritic lesions, collagenase-1 (matrix metalloproteinase-1) and collagenase-3 (matrix metalloproteinase-13) mediate the irreversible destruction of cartilage, suggesting that these enzymes are therapeutic targets. We describe the role of metalloproteinases in the destruction of connective tissues in arthritis and the treatment strategies that have been developed to block matrix metalloproteinases in an attempt to prevent this destruction. We also discuss novel compounds that may selectively inhibit these cartilage-degrading enzymes, providing opportunities to develop new therapeutic approaches.

• Authors: Kimberlee S Mix, Michael B Sporn, Constance E Brinckerhoff, David Eyre, David J Schurman
• Journal: Clinical orthopaedics and related research (Clin Orthop Relat Res) Issue 427 Suppl Pg. S129-37 (Oct 2004) ISSN: 0009-921X [Print] United States
• PMID: 15480055 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Matrix Metalloproteinase Inhibitors
• Matrix Metalloproteinases

Topics

• Animals
• Arthritis (drug therapy, etiology, genetics)
• Gene Expression Regulation (drug effects)
• Humans
• Matrix Metalloproteinase Inhibitors
• Matrix Metalloproteinases (genetics)