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Osteoarthritis is a common joint disease for which there are currently no disease-modifying drugs available. Degradation of the cartilage extracellular matrix is a central feature of the disease and is widely thought to be mediated by proteinases that degrade structural components of the matrix, primarily aggrecan and collagen. Studies on transgenic mice have confirmed the central role of Adamalysin with Thrombospondin Motifs 5 (ADAMTS-5) in aggrecan degradation, and the collagenolytic matrix metalloproteinase MMP-13 in collagen degradation. This review discusses recent advances in current understanding of the mechanisms regulating expression of these key enzymes, as well as reviewing the roles of other proteinases in cartilage destruction. This article is part of a Special Issue entitled: Proteolysis 50 years after the discovery of lysosome.

Type

Journal article

Journal

Biochimica et biophysica acta

Publication Date

01/2012

Volume

1824

Pages

133 - 145

Addresses

The Kennedy Institute of Rheumatology Division, Imperial College London, London, UK. linda.troeberg@kennedy.ox.ax.uk

Keywords

Cartilage, Extracellular Matrix, Animals, Humans, Mice, Osteoarthritis, Peptide Hydrolases, Collagenases, Matrix Metalloproteinases, Gene Expression Regulation, Enzymologic, Models, Biological, ADAM Proteins, Proteolysis