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Updated: Aug 13, 2026
An Ex Vivo Tissue Culture Model of Cartilage Remodeling in Bovine Knee Explants
Published on: November 3, 2019
Interleukin-4, an inhibitor of cartilage breakdown in bovine articular cartilage explants
L A Yeh1, A J Augustine, P Lee
1Department of Enzyme Biochemistry, OsteoArthritis Sciences, Inc., Cambridge, MA 02139, USA.
Objective:
To determine the ability of interleukin-4 (IL-4) to inhibit the degradation of proteoglycan in bovine articular cartilage explants stimulated by human interleukin-1 (IL-1 alpha), tumor necrosis factor (TNF-alpha), a combination of TNF-alpha and IL-1 alpha, and lipopolysaccharide (LPS).
Methods:
35SO4 radiolabelled bovine radiocarpal cartilage explants were treated with IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS, plus various concentrations of IL-4 for 72 h. Proteoglycan released to the media was analyzed by scintillation counting and composite gel electrophoresis. Media samples were also analyzed by Western immunoblotting for metalloproteinases and TIMP.
Results:
IL-4 significantly reduced the cartilage proteoglycan degradation induced by IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS (50% inhibitory concentration, IC50 for IL-4 ranged from about 15 to 50 ng/ml). Western blotting showed that media stromelysin levels were increased by IL-1 alpha, TNF-alpha, and LPS, but that IL-4 had no observable effect. Composite gel electrophoresis demonstrated quantitative and qualitative differences in proteoglycan degradation after IL-4 treatment.
Conclusion:
IL-4 has a potent inhibitory effect on cartilage degradation after stimulation with IL-1 alpha, TNF-alpha, TNF-alpha plus IL-1 alpha, or LPS. These results suggest that IL-4 should be investigated further for therapeutic value as a chondroprotective agent for the treatment of arthritis.
