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.
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Research Article|
December 01 1994
Neutrophil collagenase (MMP-8) cleaves at the aggrecanase site E373–A374 in the interglobular domain of cartilage aggrecan
A J Fosang;
A J Fosang
*University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, 3050, Australia
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K Last;
K Last
*University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, 3050, Australia
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P J Neame;
P J Neame
†Shriners Hospital for Crippled Children, Tampa, Florida 33612, U.S.A
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G Murphy;
G Murphy
‡Strangeways Research Laboratory, Cambridge CB1 4RN, U.K.
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V Knäuper;
V Knäuper
†Shriners Hospital for Crippled Children, Tampa, Florida 33612, U.S.A
§Universitat Bielefeld, Fakultat fur Chemie, Lehrstuhl fur Biochemie, W-4800 Bielefeld, Germany
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H Tschesche;
H Tschesche
§Universitat Bielefeld, Fakultat fur Chemie, Lehrstuhl fur Biochemie, W-4800 Bielefeld, Germany
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C E Hughes;
C E Hughes
∥Universiy of north carolina Department of orthopaedics, chapel Hill, NC, USA
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B Caterson;
B Caterson
∥Universiy of north carolina Department of orthopaedics, chapel Hill, NC, USA
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T E Hardingham
T E Hardingham
Ƃkennedy institute of Rheumatology, Hammersmith, london W6 7DW, UK
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Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1994 The Biochemical Society, London
1994
Biochem J (1994) 304 (2): 347–351.
Citation
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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