The action of human articular-cartilage metalloproteinase on proteoglycan and link protein. Similarities between products of degradation in situ and in vitro.
Interleukin 1 stimulation of human articular cartilage in organ culture produced the concomitant release of proteoglycan fragments and latent metalloproteinase. The released fragments ranged in size from that of almost intact proteoglycan subunits to the product of limiting digestion generated by the activated metalloproteinase. None of the fragments possessed the ability to interact with hyaluronic acid. Analysis of proteoglycan aggregate digested with the activated metalloproteinase showed that isolated hyaluronic acid-binding regions were produced from the proteoglycan subunits, and that the two higher-Mr link-protein components (Mr 48,000 and 44,000) were converted into the lowest-Mr component (Mr 41,000). Link protein extracted from cartilage under stimulation with interleukin 1 showed a similar conversion. These results suggest that interleukin 1 stimulates the release of latent metalloproteinase from chondrocytes and that a proportion of the enzyme is activated in situ in the cartilage matrix. The mode of action of the activated enzyme is compatible with a role in the changes in proteoglycan structure seen in aging.
D002358:Cartilage, Articular / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D046911:Macromolecular Substances; D008666:Metalloendopeptidases; D010662:Phenylmercuric Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D000099249:Proteoglycan Link Protein
D010450:Endopeptidases; D016326:Extracellular Matrix Proteins; D007375:Interleukin-1; D046911:Macromolecular Substances; D008666:Metalloendopeptidases; D010662:Phenylmercuric Acetate; D011506:Proteins; D011509:Proteoglycans; D013439:Sulfhydryl Reagents; D000099249:Proteoglycan Link Protein; C010024:4-aminophenylmercuriacetate