Native and recombinant neutrophil collagenase (MMP-8) was shown to cleave at the E373-A374 ‘aggrecanase’ site in the interglobular domain of aggrecan. The time course of digestion in vitro showed that MMP-8 cleaved initially at N341-F342, the predominant metalloproteinase site, before cleaving at the E373-A374 site. A synthetic peptide, IPENFFG, inhibited cleavage at E373-A374 but not N341-F342 in vitro, indicating that the E373-A374 sequence was a less preferred site for MMP-8 cleavage than N341-F342. IPENFFG also inhibited release of A374 RGSVI fragments from cartilage in explant culture, suggesting that a metalloproteinase cleaved at the aggrecanase site in situ. The possibility remains that ‘aggrecanase’ may be a metalloproteinase in cartilage.
Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373–A374 in the interglobular domain of cartilage aggrecan
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A J Fosang, K Last, P J Neame, G Murphy, V Knäuper, H Tschesche, C E Hughes, B Caterson, T E Hardingham; Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373–A374 in the interglobular domain of cartilage aggrecan. Biochem J 1 December 1994; 304 (2): 347–351. doi: https://doi.org/10.1042/bj3040347
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