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

Abstract

Tumor necrosis factor alpha (TNF alpha) 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 TNF alpha produced putative "cartilage-specific" proteoglycans identified by density gradient centrifugation under dissociative conditions. Although TNF alpha decreased the synthesis of the proteoglycans, it did not change their monomeric size, which is a marker of cartilage phenotypes. Moreover, TNF alpha did not affect the responsiveness to parathyroid hormone, insulin-like growth factor I, or transforming growth factor beta, which is known to stimulate GAG synthesis in cultured chondrocytes. TNF alpha 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 TNF alpha 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, TNF alpha promotes the proliferation of chondrocytes while suppressing their further differentiation at the stage of synthesis of cartilage-specific proteoglycans.