Effects of tumor necrosis factor α on proliferation and expression of differentiated phenotypes in rabbit costal chondrocytes in culture

Tumor necrosis factor α (TNFα) decreased the synthesis of glycosaminoglycan (GAG) in rabbit costal chondrocytes in culture, but did not stimulate the release of GAG from cell layers. Like chondrocytes cultured in control medium, chondrocytes cultured in the presence of TNFα produced putative "cartilage-specific" proteoglycans identified by density gradient centrifugation under dissociative conditions. Although TNFα decreased the synthesis of the proteoglycans, it did not change their monomeric size, which is a marker of cartilage phenotypes. Moreover, TNFα did not affect the responsiveness to parathyroid hormone, insulin-like growth factor I, or transforming growth factor β, which is known to stimulate GAG synthesis in cultured chondrocytes. TNFα decreased the alkaline phosphatase activity in the chondrocytes dose dependently. On the other hand, it stimulated their DNA synthesis slightly, but significantly. The stimulatory effect of TNFα on DNA synthesis was potentiated by fibroblast growth factor, epidermal growth factor, and fetal bovine serum. These findings suggest that in the presence of hormones and growth factors, TNFα promotes the proliferation of chondrocytes while suppressing their further differentiation at the stage of synthesis of cartilage-specific proteoglycans.