Synergistic effect of transforming growth factor β and fibroblast growth factor on DNA synthesis in chick growth plate chondrocytes

Transforming growth factor β and fibroblast growth factor are mitogens for chick growth plate chondrocytes. TGF‐β stimulated a 3.5‐fold increase, and FGF a 13.5‐fold increase in the rate of thymidine incorporation after a 24 h exposure. TGF‐β and FGF were synergistic in chondrocytes, causing a 73‐fold stimulation in thymidine incorporation compared with control. This synergistic response was not dependent upon the simultaneous presence of both mitogens. Sequential exposure of chondrocytes to TGF‐β and FGF in either order reproduced in large part the synergistic interaction observed when both growth factors were present simultaneously. The time required for induction of the subsequent synergistic response was brief and, in the case of TGF‐β, corresponded to the time required for [¹²⁵I]TGF‐β receptor binding. EGF and PDGF were not mitogenic for chondrocytes, and neither of these factors enhanced the response of the cells to either TGF‐β or FGF. Finally, TGF‐β and FGF did not, either alone or in combination, elevate intracellular cAMP levels. These results emphasize the importance of examining growth factor effects in the context of other growth regulators. Furthermore, this specific and dramatic synergistic stimulation of thymidine incorporation may provide a useful tool in elucidating the mitogenic mechanism of the individual growth factors.