ADAMTS-8 exhibits aggrecanase activity and is expressed in human articular cartilage

Matrix Biol. 2004 Jul;23(4):219-30. doi: 10.1016/j.matbio.2004.05.004.


Members of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family share common structural features including a disintegrin domain, a zinc metalloprotease domain, and at least one thrombospondin motif. Aberrant expression of several of these proteins has led to an understanding of their role in human disease; however, a link to function for many has not yet been made. One such uncharacterized family member, ADAMTS-8, shares significant protein sequence homology with a subgroup of ADAMTSs that includes ADAMTS-1, ADAMTS-4, ADAMTS-5, and ADAMTS-15. Each of these proteases has been shown to cleave 'aggrecanase-susceptible' site(s) within the extracellular matrix (ECM) proteoglycan aggrecan, and ADAMTS-4 and ADAMTS-5 have been postulated to play a role in the depletion of articular cartilage in osteoarthritic disease. Based on sequence relationships, in the present study we examined the ability of ADAMTS-8 to exhibit 'aggrecanase' activity. A neoepitope monoclonal antibody (MAb; AGG-C1; anti-NITEGE373) was developed and used to demonstrate the ability of ADAMTS-8 to cleave aggrecan at the aggrecanase-susceptible Glu373-Ala374 peptide bond. In addition, expression analyses demonstrated the presence of ADAMTS-8 mRNA transcripts in normal and osteoarthritic human cartilage.

MeSH terms

  • ADAM Proteins
  • ADAMTS9 Protein
  • Aggrecans
  • Animals
  • Antibodies, Monoclonal / immunology
  • Blotting, Western
  • CHO Cells
  • Cartilage, Articular / enzymology*
  • Cricetinae
  • Cricetulus
  • Endopeptidases / metabolism*
  • Enzyme-Linked Immunosorbent Assay / methods
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Lectins, C-Type
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / immunology
  • Metalloendopeptidases / isolation & purification
  • Metalloendopeptidases / metabolism*
  • Osteoarthritis / metabolism
  • Polymerase Chain Reaction
  • Proteoglycans / metabolism
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Tissue Distribution


  • Aggrecans
  • Antibodies, Monoclonal
  • Extracellular Matrix Proteins
  • Lectins, C-Type
  • Proteoglycans
  • RNA, Messenger
  • Endopeptidases
  • ADAM Proteins
  • ADAMTS9 Protein
  • ADAMTS9 protein, human
  • Metalloendopeptidases
  • aggrecanase