title: An aggrecan-degrading activity associated with chondrocyte membranes.
abstract: The breakdown of aggrecan in cartilage is, in part, mediated by an enzyme named aggrecanase that cleaves within the interglobular domain of the molecule between a glutamic residue and an alanine residue. Although the enzyme cleavage site has been identified, the identity, characteristics and localization of this enzyme remain unclear. We have demonstrated that membranes isolated from stimulated chondrocytes are able to generate aggrecan fragments that are labelled by an antibody that recognizes the new N-terminus formed by aggrecanase activity. It was further shown that the membrane activity was a metalloproteinase but was not inhibited by the naturally occurring matrix metalloproteinase (MMP) inhibitors, TIMPs 1 and 2. These results show that an aggrecanase activity is associated with the membranes of the chondrocytes and is a metalloproteinase, but might not be a member of the MMP family.
authors.affiliation: Department of Rheumatology, School of Clinical and Medical Sciences, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Billington
authors.forename: I M
authors.initials: IM
authors.lastname: Clark
authors.forename: T E
authors.initials: TE
authors.lastname: Cawston
mesh_terms: D053674:Aggrecans; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D019902:Chondrocytes / Q000201:enzymology / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D006868:Hydrolysis; D007375:Interleukin-1 / Q000494:pharmacology; D037181:Lectins, C-Type; D008969:Molecular Sequence Data; D053683:Oncostatin M; D010455:Peptides / Q000494:pharmacology; D011509:Proteoglycans / Q000378:metabolism*; D013379:Substrate Specificity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000494:pharmacology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology
chemical_list: D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D037181:Lectins, C-Type; D010455:Peptides; D011509:Proteoglycans; D019715:Tissue Inhibitor of Metalloproteinase-1; D053683:Oncostatin M; D019716:Tissue Inhibitor of Metalloproteinase-2; D010450:Endopeptidases; C083641:aggrecanase