Articular cartilage breakdown in a lapine model of osteoarthritis. Action of glycosaminoglycan polysulfate ester (GAGPS) on proteoglycan degrading enzyme activity, hexuronate, and cell counts.
The action of glycosaminoglycan polysulfate (GAGPS) on the development of meniscectomy-induced "osteoarthritis" in rabbits was studied in respect to enzyme activities in articular cartilage. Rabbits were treated for 11 weeks beginning one week after meniscectomy and "therapeutic" treatment from the 12th to the 20th week after meniscectomy, following presumed development of lesions. The experimental design was identical to that of another study, in which prevention of cartilage erosions was indicated by gross morphologic and histologic parameters. In the present study, enzyme activities were measured for neutral metalloprotease(s), (NMPE), serine protease(s) and thiol protease(s) in extracts from cartilage obtained at sacrifice. Control cartilage enzyme activities consisted of intact normal and surgically altered rabbits treated with saline matched for each regimen. In the positive controls, there were highly significant elevations of NMPE active on proteoglycans and serine protease activity per milligram of wet cartilage at 20 weeks, as well a highly significant elevation of metalloprotease 12 weeks after operation. A significantly lower level of active NMPE was found in experimental groups compared with positive controls. Cell counts per unit volume were doubled in the treated versus untreated cartilages. Hexuronate as an index of proteoglycan content was reduced in positive controls and restored to normal levels or higher with the use of GAGPS in both prophylactic and therapeutic regimens.
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D003546:Cysteine Endopeptidases; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006603:Hexuronic Acids / Q000378:metabolism; D008666:Metalloendopeptidases; D015260:Neprilysin; D010003:Osteoarthritis / Q000378:metabolism*; D011480:Protease Inhibitors; D011817:Rabbits; D012697:Serine Endopeptidases
D006025:Glycosaminoglycans; D006603:Hexuronic Acids; D011480:Protease Inhibitors; C013786:A73025; D010450:Endopeptidases; C022474:proteoglycan-degrading metalloendopeptidases; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin