Articular chondrocytes and synoviocytes in culture: influence of antioxidants on lipid peroxidation and proliferation.

Chondrocytes and synoviocytes are the main cell types in articular joints. Articular cartilage is fed by synoviocytes via synovial fluid and has a low partial oxygen pressure. Thus, chondrocytes show oxygen radical protective mechanisms in vivo and are unprotected against these factors under common culture conditions. We investigated the influence of ascorbic acid, Fe2+, glutathione and alpha-tocopherol on lipid peroxidation and proliferation of rat articular chondrocytes and rabbit synoviocytes (HIG-82) in vitro. A combination of ascorbic acid and Fe2+ induced the production of thiobarbituric acid-reactive material as a marker of radical-mediated lipid peroxidation in homogenates and/or supernatants of cultured chondrocytes and synoviocytes. The amount of lipid peroxidation of chondrocytes was about 3-fold higher than that of synoviocytes. Ascorbic acid or Fe2+ alone had no significant influence on the production of thiobarbituric acid-reactive material. Lipid peroxidation could be abolished by addition of the radical scavenger alpha-tocopherol, whereas glutathione had no effect. 25-50 microM alpha-tocopherol decreased the ascorbic acid-(100 micrograms/ml) and Fe(2+)-(3 microM) induced lipid peroxidation to a basal level. Moreover, ascorbic acid inhibited the proliferation of rat chondrocytes and rabbit synoviocytes measured by [3H]-thymidine incorporation. Alpha-tocopherol and glutathione had no influence on the proliferation of chondrocytes but alpha-tocopherol decreased the growth of synoviocytes and increased the anti-proliferative effect of ascorbic acid on these cells. The importance of these findings for the use of ascorbic acid, glutathione and alpha-tocopherol in chondrocyte and synoviocyte cultures, or the influence of these molecules on the etiology and treatment of articular diseases will be discussed.