Article Text
Abstract
A role for metalloproteinases in the pathological destruction in diseases such as rheumatoid arthritis and osteoarthritis, and the irreversible nature of the ensuing cartilage and bone damage, have been the focus of much investigation for several decades. This has led to the development of broad spectrum metalloproteinase inhibitors as potential therapeutics. More recently it has been appreciated that several families of zinc dependent proteinases play significant and varied roles in the biology of the resident cells in these tissues, orchestrating development, remodelling, and subsequent pathological processes. They also play key roles in the activity of inflammatory cells. The task of elucidating the precise role of individual metalloproteinases is therefore a burgeoning necessity for the final design of metalloproteinase inhibitors if they are to be employed as therapeutic agents.
- ADAM, disintegrin metalloproteinase
- ADAM TS, disintegrin metalloproteinase with thrombospondin repeats
- ECM, extracellular matrix
- MMP, matrix metalloproteinase
- MT, membrane type
- TACE, tumour necrosis factor α converting enzyme
- TIMP, tissue inhibitor of metalloproteinases
- MMP
- ADAM
- ADAM-TS
- TIMP
- inhibitor
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Footnotes
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Work in the authors’ laboratory is funded by the Medical Research Council, Cancer Research UK, and the European Union Framework 5 and 6 Programmes (QLK3-CT2002-02316 and project LSHC-CT-2003-503297, respectively).
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Competing interests: none declared