INHIBITORY EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR ON CHONDROCYTE DIFFERENTIATION

The role of basic fibroblast growth factor (bFGF) and insulin-like gro wth factor I (IGF-I) in cartilage growth,vas studied in primary cultur es of rat rib growth plate chondrocytes. Growth factors effects on exp ression of the proto-oncogene c-fos, DNA synthesis, differentiation, a nd morphological changes were analyzed by in situ hybridization, H-3-t hymidine incorporation, and light and fluorescence microscopy. In seru m-deprived cells, bFGF induced a transient expression of c-fos with a maximal effect 15-30 minutes after stimulation. After 24 h of culture it had a slightly lower stimulatory effect on DNA synthesis than IGF-I , but became a significantly more potent mitogen than IGF-I after 48 a nd 72 h. The stimulatory effect of bFGF on DNA synthesis coincided wit h a decrease in collagen type II and IGF-II expression. In contrast, I GF-I alone stimulated expression of these genes. In bFGF-treated cultu res, cell morphology and the appearance of actin filaments was changed . Polygonal chondrocytes became elongated, fibroblast-like, and the sm ooth actin filaments were brush-like and disrupted. Addition of IGF-I reduced these changes without affecting c-fos expression induced by bF GF. Our results suggest that bFGF stimulates cell proliferation by pre venting terminal differentiation of chondrocytes. This effect is media ted by induction of c-fos expression and a decrease in the steady-stat e levels of transcripts for collagen II and IGF-II.