Crabb I D, O'Keefe R J, Puzas J E, Rosier R N
Department of Orthopaedics, University of Rochester, NY 14642.
J Bone Miner Res. 1990 Nov;5(11):1105-12. doi: 10.1002/jbmr.5650051103.
Transforming growth factor beta and fibroblast growth factor are mitogens for chick growth plate chondrocytes. TGF-beta 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-beta 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-beta 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-beta, corresponded to the time required for [125I]TGF-beta receptor binding. EGF and PDGF were not mitogenic for chondrocytes, and neither of these factors enhanced the response of the cells to either TGF-beta or FGF. Finally, TGF-beta 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.
转化生长因子β和成纤维细胞生长因子是鸡生长板软骨细胞的促有丝分裂原。在24小时暴露后，转化生长因子β使胸苷掺入率增加3.5倍，成纤维细胞生长因子使其增加13.5倍。转化生长因子β和成纤维细胞生长因子在软骨细胞中具有协同作用，与对照组相比，胸苷掺入增加了73倍。这种协同反应并不依赖于两种促有丝分裂原同时存在。以任何顺序将软骨细胞先后暴露于转化生长因子β和成纤维细胞生长因子中，在很大程度上重现了两种生长因子同时存在时观察到的协同相互作用。诱导随后协同反应所需的时间很短，就转化生长因子β而言，与[125I]转化生长因子β受体结合所需的时间相对应。表皮生长因子和血小板衍生生长因子对软骨细胞没有促有丝分裂作用，且这两种因子均未增强细胞对转化生长因子β或成纤维细胞生长因子的反应。最后，转化生长因子β和成纤维细胞生长因子单独或联合使用均未提高细胞内cAMP水平。这些结果强调了在其他生长调节因子的背景下研究生长因子作用的重要性。此外，这种对胸苷掺入的特异性和显著的协同刺激可能为阐明单个生长因子的促有丝分裂机制提供一个有用的工具。
