Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells
Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells
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Smads、p38 和 ERK1/2 参与 BMP9 诱导的 C3H10T1/2 间充质干细胞成骨分化
DOI：
10.5483/bmbrep.2012.45.4.247
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发表时间：
2012-04-30
期刊：
影响因子：
3.8
通讯作者：
Luo, Jin-yong
中科院分区：
文献类型：
--
作者：
Xu, Dao-jing;Zhao, Ying-ze;Luo, Jin-yong
尽管先前的研究已经证明BMP 9具有高度诱导间充质干细胞成骨分化的能力，但所涉及的分子机制仍有待充分阐明。在本研究中，我们发现BMP 9同时促进C3 H10 T1/2细胞中Smad 1/5/8、p38和ERK 1/2的激活。用RNA干扰敲低Smad 4可减少Smad 1/5/8的核转位，并破坏BMP 9诱导的成骨分化。BMP 9诱导的成骨分化被p38抑制剂SB 203580阻断，而被ERK 1/2抑制剂PD 98059增强。SB 203580降低了C3 H10 T1/2细胞中BMP 9激活的Smads单点化，而PD 98059刺激了Smads单点化。分别用表达靶向p38和ERK 1/2的siRNA的腺病毒复制抑制剂的作用。总之，我们的研究结果表明，Smads，p38和ERK 1/2参与BMP 9诱导的成骨分化。此外，值得注意的是，p38和ERK 1/2可能在介导BMP 9诱导的C3 H10 T1/2细胞的成骨分化中发挥相反的调节作用。[BMB报告2012; 45（4）：247-252]
Although previous studies have demonstrated that BMP9 is highly capable of inducing osteogenic differentiation of mesenchymal stem cells, the molecular mechanism involved remains to be fully elucidated. In this study, we showed that BMP9 simultaneously promotes the activation of Smad1/5/8, p38 and ERK1/2 in C3H10T1/2 cells. Knockdown of Smad4 with RNA interference reduced nuclear translocation of Smad1/5/8, and disrupted BMP9-induced osteogenic differentiation. BMP9-induced osteogenic differentiation was blocked by p38 inhibitor SB203580, whereas enhanced by ERK1/2 inhibitor PD98059. SB203580 decreased BMP9-activated Smads singling, and yet PD98059 stimulated Smads singling in C3H10T1/2 cells. The effects of inhibitor were reproduced with adenovirus expressing si RNA targeted p38 and ERK1/2, respectively. Taken together, our findings revealed that Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation. Also, it is noteworthy that p38 and ERK1/2 may play opposing regulatory roles in mediating BMP9-induced osteogenic differentiation of C3H10T1/2 cells. [BMB reports 2012; 45(4): 247-252]