Cartilage degradation by neutral proteoglycanases in experimental osteoarthritis. Suppression by steroids.
In this study, we sought to determine the role of neutral proteases in cartilage matrix proteoglycan degradation, which occurs during the early stages of experimental osteoarthritis. The anterior cruciate ligament was transected in the right knees of 33 dogs. Their left knees served as sham operated controls. The animals were killed 2, 4, 8, and 12 weeks after surgery. Six dogs were treated with oral prednisone and then killed 4 weeks after surgery. Cartilage specimens from medial and lateral tibial plateaus were analyzed for DNA, proteoglycan content, and neutral proteoglycan degrading activity. No significant differences in cartilage DNA and proteoglycan content were observed among the dogs that had surgery, the controls, and the prednisone-treated animals. Total neutral metalloproteoglycan-degrading enzyme (NMPE) activity, determined by direct tissue assay, was significantly higher at all time points in osteoarthritic cartilage than in control cartilage. The active form of NMPE was significantly higher in osteoarthritic cartilage than in control cartilage at 2, 4, and 8 weeks in lateral plateaus and at 2 and 4 weeks in medial plateaus. Treatment for 4 weeks with prednisone (0.20-0.25 mg/kg/day) blocked the increased NMPE activity in osteoarthritic cartilage. The increase in the total and active neutral proteoglycanases supports the hypothesis that these enzymes are involved in early osteoarthritis. The synthesis of NMPE appears to be controlled by stimulating factors released by the synovium.
D000818:Animals; D002358:Cartilage, Articular / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004285:Dogs; D010450:Endopeptidases / Q000378:metabolism*; D008666:Metalloendopeptidases; D010003:Osteoarthritis / Q000188:drug therapy / Q000378:metabolism*; D011241:Prednisone / Q000627:therapeutic use; D011509:Proteoglycans / Q000378:metabolism; D012697:Serine Endopeptidases; D014574:Uronic Acids / Q000032:analysis
D011509:Proteoglycans; D014574:Uronic Acids; D004247:DNA; D010450:Endopeptidases; C022474:proteoglycan-degrading metalloendopeptidases; D012697:Serine Endopeptidases; D008666:Metalloendopeptidases; D011241:Prednisone