title: Metalloproteinase production by rabbit articular cartilage: comparison of the effects of interleukin-1 alpha in vitro and in vivo.
abstract: To assess the effects of interleukin-1 on intact To assess the effects of interleukin-1 on intact articular cartilage in vitro, explants from young and adult rabbits were cultured with interleukin-1 and the distributions of the matrix metalloproteinases and tissue inhibitor of metalloproteinases (TIMP-1) were investigated by indirect immunofluorescence microscopy. One to 2-week-old cartilage chondrocytes synthesized collagenase in response to pure or crude interleukin-1 (monocyte conditioned medium), with subarticular cells most responsive. Collagenase synthesis was not stimulated in adult articular chondrocytes when explants were treated with either pure or crude interleukin-1. Stromelysin, gelatinase and TIMP-1 could not be demonstrated within any zone of the cartilage, indicating that their synthesis was not stimulated by either pure or crude interleukin-1. The addition of fibroblast growth factors, either alone or in combination with interleukin-1, did not modify these responses. These results contrast markedly with observations on cultured chondrocyte monolayers, where interleukin-1 treatment induces near co-ordinate expression of metalloproteinases. To assess the effects of interleukin-1 in vivo, it was injected into adult rabbit knee joint spaces and the articular cartilage subsequently analysed for evidence of altered metalloproteinase production by immunocytochemistry. No significant increase in metalloproteinase or TIMP-1 synthesis by chondrocytes was detected, although the cartilage matrix showed a marked loss of toluidine blue metachromasia. We conclude that metalloproteinases are not involved in the rapid loss of proteoglycan from cartilage matrix in these situations.
authors.affiliation: Department of Cell and Molecular Biology, Strangeways Research Laboratory, Cambridge, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Hembry
authors.forename: M R
authors.initials: MR
authors.lastname: Bagga
authors.forename: J T
authors.initials: JT
authors.lastname: Dingle
authors.forename: P P
authors.initials: PP
authors.lastname: Thomas
authors.forename: J J
authors.initials: JJ
authors.lastname: Reynolds
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D017364:Collagenases / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018093:Gelatinases / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis*; D011817:Rabbits; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine; D019714:Tissue Inhibitor of Metalloproteinases
chemical_list: D006023:Glycoproteins; D007375:Interleukin-1; D011994:Recombinant Proteins; D019714:Tissue Inhibitor of Metalloproteinases; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D003907:Dexamethasone; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3