Inhibition of ADAMTS4 (aggrecanase-1) by tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4)

Gakuji Hashimoto, Takanori Aoki, Hiroyuki Nakamura, Kazuhiko Tanzawa, Yasunori Okada

Research output: Contribution to journalArticlepeer-review

172 Citations (Scopus)


ADAMTS4 (aggrecanase-1) is considered to play a key role in the degradation of aggrecan in arthritides. The inhibitory activity of tissue inhibitors of metalloproteinases (TIMPs) to ADAMTS4 was examined in an assay using aggrecan substrate. Among the four TIMPs, TIMP-3 inhibited the activity most efficiently with an IC50 value of 7.9 nM, which was at least 44-fold lower than that of TIMP-1 (350 nM) and TIMP-2 (420 nM) and > 250-fold less than that of TIMP-4 (2 μM for 35% inhibition). These results suggest that TIMP-3 is a potent inhibitor against the aggrecanase activity of ADAMTS4 in vivo.

Original languageEnglish
Pages (from-to)192-195
Number of pages4
JournalFEBS Letters
Issue number3
Publication statusPublished - 2001 Apr 13
Externally publishedYes


  • A disintegrin and metalloproteinase
  • A disintegrin and metalloproteinase with thrombospondin motifs 4
  • Aggrecan degradation
  • Aggrecanase
  • Tissue inhibitor of metalloproteinases

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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