Fibroblast growth factor 2 inhibits bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells by repressing Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2.
Fibroblast growth factor 2 inhibits bone morphogenetic protein 9-induced osteogenic differentiation of mesenchymal stem cells by repressing Smads signaling and subsequently reducing Smads dependent up-regulation of ALK1 and ALK2.
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DOI：
10.1016/j.biocel.2013.05.005
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发表时间：
2013-08
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影响因子：
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通讯作者：
Tao Song;Wen-juan Wang;Jing Xu;Dan Zhao;Q. Dong;Li Li-Li;Xue Yang;Xinglian Duan;Yi-wen Liang;Yan-Bing Xiao;Jin Wang;Juan-wen He;Mingyu Tang;Jian Wang;Jinyong Luo
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文献类型：
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作者：
Tao Song;Wen-juan Wang;Jing Xu;Dan Zhao;Q. Dong;Li Li-Li;Xue Yang;Xinglian Duan;Yi-wen Liang;Yan-Bing Xiao;Jin Wang;Juan-wen He;Mingyu Tang;Jian Wang;Jinyong Luo
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在骨组织工程中的应用的关键问题。BMP9高度促进MSC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FGF 2对BMP 9诱导的MSCs成骨分化的详细影响。发现FGF2通过阻断BMP 9诱导的Smads信号传导并随后减少MSC中ALK 1和ALK 2的Smads依赖性上调来抑制BMP 9诱导的成骨分化。这种作用被ALK 1和ALK 2的外源性表达所拯救，ALK 1和ALK 2被证明是BMP 9的受体。我们的研究结果为解释FGF2抑制BMP 9诱导的MSC成骨分化的机制提供了线索。FGF2和BMP 9之间的这种相互作用在将来BMP 9用于骨折修复的治疗目的中应得到强调。
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.