Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 40016, PR China.
Int J Biochem Cell Biol. 2013 Aug;45(8):1639-46. doi: 10.1016/j.biocel.2013.05.005. Epub 2013 May 13.
Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of mesenchymal stem cells (MSCs) and BMPs in bone tissue engineering. BMP9 is highly capable of promoting osteogenic differentiation of MSCs. Fibroblast growth factor 2 (FGF2) is abundantly secreted during the healing process of fractures or in surgery bone sites. Herein, we explore the detail effect of FGF2 on BMP9-induced osteogenic differentiation of MSCs. It was found that FGF2 inhibited BMP9-induced osteogenic differentiation by blocking BMP9-induced Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2 in MSCs. This effect was rescued by exogenous expression of ALK1 and ALK2, which are proved to be receptors for BMP9. Our results discovered a clue to explain the mechanism involved in the inhibitory effect of FGF2 on BMP9-induced osteogenic differentiation of MSCs. This crosstalk between FGF2 and BMP9 should be emphasized in the future use of BMP9 in therapeutic purpose of fracture repair.
了解生长因子和骨形态发生蛋白（BMPs）信号之间的相互作用仍然是优化间充质干细胞（MSCs）和 BMPs 在骨组织工程中应用的关键问题。BMP9 非常能够促进 MSCs 的成骨分化。成纤维细胞生长因子 2（FGF2）在骨折愈合过程中或手术骨部位大量分泌。在此，我们探讨了 FGF2 对 BMP9 诱导的 MSCs 成骨分化的详细影响。结果发现，FGF2 通过阻断 BMP9 诱导的 Smads 信号转导，从而减少 Smads 依赖性上调 MSCs 中的 ALK1 和 ALK2，抑制 BMP9 诱导的成骨分化。通过外源表达 ALK1 和 ALK2 可以挽救这种效应，ALK1 和 ALK2 被证明是 BMP9 的受体。我们的结果发现了解释 FGF2 抑制 BMP9 诱导的 MSCs 成骨分化的机制的线索。在未来 BMP9 用于骨折修复的治疗目的时，应强调 FGF2 和 BMP9 之间的这种串扰。
