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ADAMTS-4 and ADAMTS-5

Aggrecanases

  • Chapter
The ADAM Family of Proteases

Part of the book series: Proteases in Biology and Disease ((PBAD,volume 4))

Abstract

Osteoarthritis (OA) is characterized by articular cartilage erosion as a consequence of proteolytic cleavage of its two major functional macromolecules, type II collagen and aggrecan. Aggrecan degradation in OA and rheumatoid arthritis is attributed to cleavage at the Glu373-Ala374 bond by the aggrecanases. Two aggrecanases, purified from IL-1-stimulated cartilage explants, were identified as members of the a disintegrin and metalloproteinase with thrombospondin m p otifs (ADAMTS) family, ADAMTS-4 and ADAMTS-5, and work from a number of groups has begun to provide insight into the molecular basis for the role of these proteases in aggrecan catabolism. The expression of the aggrecanases can be up-regulated by a number of factors including cytokines, retinoic acid, and fragments of the extracellular matrix molecule, fibronectin. To date two endogenous inhibitors of aggrecanase activity have been identified, TIMP-3 and α2-macroglobulin. However, recent studies suggest that activity may also be controlled by the ability of aggrecanases to access the core protein of the heavily glycosylated aggrecan substrate. In addition, post-translational processing is another means of controlling activity of these proteases. Removal of the propeptide domain is required for activity as well as potentially C-terminal truncation. Knowledge continues to accumulate on the expression pattern of these proteases in different tissues and their potential role in normal physiological mechanisms and in disease.

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Authors and Affiliations

  1. Joint Biology, Pfizer Global Research and Development, St Louis Research Laboratories, 700 Chesterfield Parkway West, St Louis, MO, USA

    Anne-Marie Malfait, Micky Tortorella & Elizabeth Arner

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  1. Anne-Marie Malfait
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  2. Micky Tortorella
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  3. Elizabeth Arner
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  1. University of Leeds, UK

    Nigel M. Hooper

  2. University of Magdeburg, Germany

    Uwe Lendeckel

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Malfait, AM., Tortorella, M., Arner, E. (2005). ADAMTS-4 and ADAMTS-5. In: Hooper, N.M., Lendeckel, U. (eds) The ADAM Family of Proteases. Proteases in Biology and Disease, vol 4. Springer, Boston, MA. https://doi.org/10.1007/0-387-25151-0_14

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