Activation of JNKs is essential for BMP9-induced osteogenic differentiation of mesenchymal stem cells.

Activation of JNKs is essential for BMP9-induced osteogenic differentiation of mesenchymal stem cells.
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JNK 的激活对于 BMP9 诱导的间充质干细胞成骨分化至关重要

DOI:
10.5483/bmbrep.2013.46.8.266
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发表时间:
2013-08
期刊:
影响因子:
3.8
通讯作者:
Luo JY
Luo JY
中科院分区:
生物学3区
文献类型:
--
作者:
Zhao YF;Xu J;Wang WJ;Wang J;He JW;Li L;Dong Q;Xiao Y;Duan XL;Yang X;Liang YW;Song T;Tang M;Zhao D;Luo JY

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尽管BMP9对骨髓间充质干细胞(MSCs)有很强的成骨分化作用,但其分子机制仍未完全阐明。在这里,我们探讨JNKs(c-jun氨基末端蛋白)在BMP9诱导的MSCs成骨分化中的可能参与和具体作用。结果表明,BMP9可刺激MSCs中JNKs的活化。JNKs抑制剂SP600125可显著抑制BMP9诱导的MSCs成骨分化。SP600125可抑制BMP9激活的Smads信号转导通路。通过表达靶向JNKs的siRNA的腺病毒复制抑制物的作用。综上所述,我们的结果表明JNKs在BMP9诱导的MSCs成骨分化中被激活。然而,最值得注意的是,抑制JNKs的活性导致了BMP9诱导的MSCs成骨分化的减少,这意味着JNKs的激活是BMP9成骨诱导活性所必需的。[BMB报告2013;46(8):422-427]
Although BMP9 is highly capable of promoting osteogenic differentiation of mesenchymal stem cell (MSCs), the molecular mechanism involved remains to be fully elucidated. Here, we explore the possible involvement and detail role of JNKs (c-Jun N-terminal kinases) in BMP9-induced osteogenic differentiation of MSCs. It was found that BMP9 stimulated the activation of JNKs in MSCs. BMP9-induced osteogenic differentiation of MSCs was dramatically inhibited by JNKs inhibitor SP600125. Moreover, BMP9-activated Smads signaling was decreased by SP600125 treatment in MSCs. The effects of inhibitor are reproduced with adenoviruses expressing siRNA targeted JNKs. Taken together, our results revealed that JNKs was activated in BMP9-induced osteogenic differentiation of MSCs. What is most noteworthy, however, is that inhibition of JNKs activity resulted in reduction of BMP9-induced osteogenic differentiation of MSCs, implying that activation of JNKs is essential for BMP9 osteoinductive activity. [BMB Reports 2013; 46(8):422-427]
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