Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A(374) in the interglobular domain of cartilage aggrecan

Fosang, A J, Last, K, Neame, P J, Murphy, G, Knauper, Vera ORCID: https://orcid.org/0000-0002-3965-9924, Tschesche, H, Hughes, C E, Caterson, B and Hardingham, T E 1994. Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373-A(374) in the interglobular domain of cartilage aggrecan. Biochemical Journal 304 (2) , pp. 347-351. 10.1042/bj3040347

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Dentistry
Publisher:	Portland Press
ISSN:	0264-6021
Last Modified:	15 Sep 2023 09:56
URI:	https://orca.cardiff.ac.uk/id/eprint/161597

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