Abstract: The effects of copper and zinc on cathepsin B activity, chondrocytes behaviour and matrix turnover by articular cartilage were investigated in vitro using normal horse cartilage co-cultured with synovial tissue. Proteoglycan (PG) depletion was assessed by toluidine blue staining. Co-culture cartilage expressed elevated levels and activity of the PG-degrading enzyme cathepsin B. Copper but not zinc was able to reduce the depletion of PG and the enzyme activity induced by the synovial tissue.