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Matrix metalloproteinase knockout studies and the potential use of matrix metalloproteinase inhibitors in the rheumatic diseases

Lookup NU author(s): Dr Jenny Milner, Emeritus Professor Tim Cawston


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The matrix metalloproteinases (MMPs) comprise a family of enzymes that collectively can degrade all components of the extracellular matrix (ECM). MMPs play an important role in many physiological processes such as embryonic development and growth, tissue remodelling and repair. Overexpression and activation of MMPs contributes to many pathologies, including arthritis, cardiovascular disease, tumour progression and lung disease. Targeted mutagenesis has allowed investigators to examine the contribution of MMPs to these physiological and pathologic processes. In this manuscript, we will present an up-to date review of these studies. Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic diseases that result in cartilage degradation and loss of joint function. MMPs have been implicated in the collagen breakdown that contributes to joint destruction. Current available drugs to treat arthritis are predominantly directed towards the control of pain and/or the inflammation associated with joint synovitis but they do little to reduce joint destruction. Synthetic MMP inhibitors have been developed and in animal models of OA and/or RA, these agents have shown chondroprotective effects. However, results from clinical trials in RA have been equivocal, with some studies being terminated because of lack of efficacy or safety concerns. Increased understanding of the structure, regulation and function of individual MMPs may lead to more effective strategies. Approaches aimed at multiple steps of the pathogenesis of arthritis may be needed to break the chronic cycle of joint destruction. In the future, it will be important to have drugs that prevent the structural damage caused by bone and cartilage breakdown. cr 2005 Bentham Science Publishers Ltd.

Publication metadata

Author(s): Milner JM, Cawston TE

Publication type: Review

Publication status: Published

Journal: Current Drug Targets: Inflammation and Allergy

Year: 2005

Volume: 4

Issue: 3

Pages: 363-375

ISSN (print): 1871-5281

ISSN (electronic): 1568-010X


DOI: 10.2174/1568010054022141

PubMed id: 16101546