Inhibition of interleukin 1-mediated proteoglycan degradation in bovine articular cartilage explants by addition of sodium hyaluronate.
The effect of exogenous hyaluronate on normal cartilage metabolism and interleukin-1 (IL-1)-induced cartilage matrix degradation was investigated in a bovine cartilage explant culture system. Addition of hyaluronate at a concentration of 1.5 mg/ml to cartilage culture explants consistently decreased normal proteoglycan release from the matrix to a value less than that found in control cultures. Addition of 1.5 mg of hyaluronate/ml to IL-1 stimulated cartilage culture systems reduced proteoglycan release from the matrix by 83 to 113%. The reduction in control and IL-1-stimulated proteoglycan degradation by hyaluronate had a concentration-dependent trend. Evaluation of alterations in protein (enzyme) release by IL-1-stimulated chondrocytes after introduction of hyaluronate was evaluated by use of sodium dodecyl sulfate agar gel electrophoresis of cartilage-conditioned media. The quantity or the molecular weight profile of IL-1-induced proteins did not differ after introduction of hyaluronate into the culture system. Results indicate that introduction of high molecular weight hyaluronate into cartilage culture systems results in a decrease in proteoglycan release from the matrix in control systems, as well as in cultures incubated with IL-1. Because IL-1-stimulated protein synthesis by chondrocytes remains unchanged after addition of exogenous hyaluronate, the mechanism of inhibition of matrix degradation does not appear to be interference with binding of IL-1 to chondrocytes or to be inhibition of the production of neutral metalloproteases, including stromelysin.
Morris
E A
EA
Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536.
Wilcon
S
S
Treadwell
B V
BV
D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D006820:Hyaluronic Acid / Q000494:pharmacology*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis; D011509:Proteoglycans / Q000187:drug effects* / Q000378:metabolism
D007375:Interleukin-1; D011509:Proteoglycans; D006820:Hyaluronic Acid; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3