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

doi:10.1016/S0014-5793(01)02323-7

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

Department of Pathology

Research output: Contribution to journal › Article › peer-review

166 Citations (Scopus)

Abstract

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 language	English
Pages (from-to)	192-195
Number of pages	4
Journal	FEBS Letters
Volume	494
Issue number	3
DOIs	https://doi.org/10.1016/S0014-5793(01)02323-7
Publication status	Published - 2001 Apr 13

Keywords

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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10.1016/S0014-5793(01)02323-7

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

abstract = "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.",

keywords = "A disintegrin and metalloproteinase, A disintegrin and metalloproteinase with thrombospondin motifs 4, Aggrecan degradation, Aggrecanase, Tissue inhibitor of metalloproteinases",

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AU - Hashimoto, Gakuji

AU - Aoki, Takanori

AU - Nakamura, Hiroyuki

AU - Tanzawa, Kazuhiko

AU - Okada, Yasunori

PY - 2001/4/13

Y1 - 2001/4/13

N2 - 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.

AB - 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.

KW - A disintegrin and metalloproteinase

KW - A disintegrin and metalloproteinase with thrombospondin motifs 4

KW - Aggrecan degradation

KW - Aggrecanase

KW - Tissue inhibitor of metalloproteinases

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

Abstract

Keywords

ASJC Scopus subject areas

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