Stimulation by human interleukin 1 of cartilage breakdown and production of collagenase and proteoglycanase by human chondrocytes but not by human osteoblasts in vitro.
Human articular chondrocytes in culture synthesise collagenase and neutral proteoglycanase in response to addition of a 12-17 kDa protein produced by cultured human monocytes. This factor copurifies with interleukin 1, as assessed by lymphocyte activating factor activity, on gel filtration chromatography and isoelectric focusing. The interleukin 1 and chondrocyte-stimulating activities are destroyed by pretreatment of the material with phenylglyoxal. The same materials also promote the release of glycosaminoglycans from cultures of intact bovine nasal cartilage. The proteoglycanase activity release from chondrocytes appears to be a metalloproteinase because it is inhibited by EDTA and not by phenylmethylsulphonyl fluoride (PMSF), and because detection of its activity is dependent on the presence of 4-aminophenylmercuric acetate. Human osteoblast-like cells do not respond to this factor by increased proteinase production, but are stimulated to produce prostaglandins. These results suggest that interleukin 1 has activities upon non-immune cells which promote the degradation of connective tissue matrices. Human osteoblasts do not synthesise neutral collagen- and proteoglycan-degrading enzymes and thus are unlikely to be directly responsible for the matrix degradation which occurs during bone resorption.
D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D010450:Endopeptidases / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008666:Metalloendopeptidases; D051379:Mice; D008815:Mice, Inbred Strains; D003012:Microbial Collagenase / Q000235:genetics*; D009000:Monocytes / Q000502:physiology; D010006:Osteoblasts / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism
D007375:Interleukin-1; D010450:Endopeptidases; D010447:Peptide Hydrolases; C022474:proteoglycan-degrading metalloendopeptidases; D008666:Metalloendopeptidases; C030895:caseinase; D003012:Microbial Collagenase