Aggrecanases and cartilage matrix degradation

Arthritis Res Ther. 2003;5(2):94-103. doi: 10.1186/ar630. Epub 2003 Feb 14.


The loss of extracellular matrix macromolecules from the cartilage results in serious impairment of joint function. Metalloproteinases called 'aggrecanases' that cleave the Glu373-Ala374 bond of the aggrecan core protein play a key role in the early stages of cartilage destruction in rheumatoid arthritis and in osteoarthritis. Three members of the ADAMTS family of proteinases, ADAMTS-1, ADAMTS-4 and ADAMTS-5, have been identified as aggrecanases. Matrix metalloproteinases, which are also found in arthritic joints, cleave aggrecans, but at a distinct site from the aggrecanases (i.e. Asn341-Phe342). The present review discuss the enzymatic properties of the three known aggrecanases, the regulation of their activities, and their role in cartilage matrix breakdown during the development of arthritis in relation to the action of matrix metalloproteinases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • ADAM Proteins
  • ADAMTS1 Protein
  • ADAMTS4 Protein
  • ADAMTS5 Protein
  • Cartilage / enzymology*
  • Disintegrins / metabolism
  • Endopeptidases / chemistry
  • Endopeptidases / metabolism*
  • Endopeptidases / physiology
  • Extracellular Matrix / metabolism
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / chemistry
  • Metalloendopeptidases / metabolism*
  • Procollagen N-Endopeptidase
  • Protein Processing, Post-Translational
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism


  • Disintegrins
  • Tissue Inhibitor of Metalloproteinase-3
  • Endopeptidases
  • ADAM Proteins
  • ADAMTS1 Protein
  • ADAMTS1 protein, human
  • ADAMTS5 Protein
  • ADAMTS5 protein, human
  • Matrix Metalloproteinases
  • Metalloendopeptidases
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human
  • aggrecanase