Inhibition of interleukin 1-mediated proteoglycan degradation in bovine articular cartilage explants by addition of sodium hyaluronate

Elisabeth A. Morris From the Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536 (Morris, Wilcon) and Orthopedic Research Laboratories, Massachusetts General Hospital, Boston, MA 02114 (Treadwell).

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Sandra Wilcon From the Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536 (Morris, Wilcon) and Orthopedic Research Laboratories, Massachusetts General Hospital, Boston, MA 02114 (Treadwell).

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Benjamin V. Treadwell From the Department of Medicine, Tufts University School of Veterinary Medicine, North Grafton, MA 01536 (Morris, Wilcon) and Orthopedic Research Laboratories, Massachusetts General Hospital, Boston, MA 02114 (Treadwell).

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Summary

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.

Summary

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.

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