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

[摘要]

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.

[学科分类] 生物化学/生物物理

[关键词] Tissue inhibitor of metalloproteinases;A disintegrin and metalloproteinase;A disintegrin and metalloproteinase with thrombospondin motifs 4;Aggrecanase;Aggrecan degradation;ADAMTS;a disintegrin and metalloproteinase with thrombospondin motifs;CaPPS;calcium pentosan polysulfate;CBB;Coomassie brilliant blue R-250;MMP;matrix metalloproteinase;SDS–PAGE;sodium dodecyl sulfate–polyacrylamide gel electrophoresis