The role of ADAMTSs in arthritis

Abstract

The ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) family is composed of 19 proteases. These enzymes are known to play an important role in development, angiogenesis and coagulation, and their dysregulation or mutation has been implicated in disease processes such as inflammation, cancer, arthritis and atherosclerosis. In addition to a brief summary of the structural organization and functional roles of ADAMTSs in normal and pathological conditions, this review focuses on the members known to be involved in the degradation of extracellular matrix and loss of cartilage in arthritis, including the aggrecanases (with special focus on ADAMTS-4 and ADAMTS-5), and ADAMTS-7 and ADAMTS-12, both of which associate with cartilage oligomeric matrix protein (COMP), a component of cartilage extracellular matrix (ECM). Expression patterns of these metalloproteinases, as well as the regulation of their activities at multiple levels, such as their interaction with substrates, induction by pro-inflammatory cytokines, protein processing, inhibition (e.g., TIMP-3, alpha-2-macroglobulin, GEP) and activation (e.g., syndecan-4, PACE-4) are reviewed.

Keywords

ADAMTS / metalloproteinase / aggrecan / COMP / arthritis