Journal
FEBS LETTERS
Volume 494, Issue 3, Pages 192-195Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0014-5793(01)02323-7
Keywords
tissue inhibitor of metalloproteinases; A disintegrin and metalloproteinase; A disintegrin and metalloproteinase with thrombospondin motifs 4; aggrecanase; aggrecan degradation
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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) acid TIMP-2 (420 nM) and > 250-fold less than that of TIMP-4 (2 muM for 35% inhibition). These results suggest that TIMP-3 is a potent inhibitor against the aggrecanase activity of ADAMTS4 in vivo. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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