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Metalloproteinases in Cartilage Matrix Breakdown: The Roles in Rheumatoid Arthritis and Osteoarthritis

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Proteases: Structure and Function

Abstract

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the two most common joint disorders, causing pain and disability to a significant proportion of the human population. Although the etiology of the two diseases is different, a common feature is the destruction of articular cartilage, which is largely due to the elevated proteolytic enzyme activities that degrade extracellular matrix (ECM) macromolecules in the cartilage. A number of proteinases, including serine and cysteine proteinases are produced in various tissues and cells in the articular joints, but the major proteinases that degrade cartilage matrices are the matrix metalloproteinases (MMPs) and the metallproteinases with disintegrin and thrombospondin domains (ADAMTs). In addition, the metalloproteinases with a disintegrin domain (ADAMs) that shed cell surface cytokines, growth factor and their receptors play important roles in inflammatory process. The activities of these metalloproteinases are regulated by endogenous tissue inhibitors of metalloproteinases called TIMPs. This chapter introduces the members of these metalloproteinases, and discuss their structures and how they are involved in cartilage matrix degradation.

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Acknowledgements

We thank Ngee Han Lim, Alan Lyons and Rob Visse for preparation of the figures. This work is supported by grant from Arthritis Research UK, European FP7 LIVIMODE programme, NIH/NIAMS grant AR40994 (to HN), and Cancer Research UK and Medical Research Council (to GM).

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Authors and Affiliations

  1. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK

    Hideaki Nagase

  2. Department of Oncology, Cancer Research UK, Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge, CB2 0RE, UK

    Gillian Murphy

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Correspondence to Hideaki Nagase .

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  1. SCHOOL OF ENGINEERING AND SCIENCE, JACOBS UNIVERSITY BREMEN, Bremen, Germany

    Klaudia Brix

  2. Institute of Zoology, Johannes Gutenberg University Mainz, Mainz, Germany

    Walter Stöcker

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Nagase, H., Murphy, G. (2013). Metalloproteinases in Cartilage Matrix Breakdown: The Roles in Rheumatoid Arthritis and Osteoarthritis. In: Brix, K., Stöcker, W. (eds) Proteases: Structure and Function. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0885-7_13

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