2012年第39卷第12期目录
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封面故事:BMP9是目前已知的BMPs中诱导MSCs(mesenchymal stem cells,MSCs)成骨分化能力最强的一种,具有广阔的潜在临床应用价值,但BMP9调控MSCs成骨分化的信号转导体系及其调控机理却有待阐明.罗进勇等的研究发现:在MSCs中BMP9能活化ERK1/2激酶途径;当利用抑制剂抑制ERK1/2后,BMP9诱导的MSCs的早期和晚期成骨分化进一步增强,而RNA干扰导致ERK1/2基因沉默同样也可进一步促进BMP9诱导的MSCs体外成骨分化,并促进BMP9诱导的MSCs在裸鼠皮下异位成骨.因此BMP9可通过活化ERK1/2激酶从而调控MSCs成骨分化,而且其调控机制可能与影响成骨关键转录因子Runx2和Smad经典途径有关.上述结果将进一步丰富目前了解甚少的BMP9诱导和调控MSCs成骨分化的机理,为其今后在临床的应用积累实验数据.
(宋 涛,何娟文,王 锦,唐 敏,罗进勇. 阻断ERK1/2激酶可增强骨形态发生蛋白9诱导的间充质干细胞成骨分化,本期第1197~1206页)
Cover Story:In our previous reports, BMP9 has shown potent function to induce osteogenic differentiation of mesenchymal stem cells, however, the underlying molecular mechanism of BMP9-induced osteogenesis is needed to be deep explored. In this study, BMP9 was introduced into mesenchymal stem cells by recombinant adenoviruses protocol, then, in vitro and in vivo assays were conducted to evidence whether BMP9 can regulate osteogenic differentiation of mesenchymal stem cells through ERK1/2 kinase pathway. The results showed that BMP9 can activate ERK1/2 kinase through increase the phosphorylated form of ERK1/2 kinase. ERK1/2 kinase inhibitor PD98059 can increase the ALP activity, OPN expression and calcium deposition of C3H10T1/2 cells induced by BMP9. Furthermore, PD98059 also led to enhancement of Runx2 activity and activation of canonical Smad pathway stimulated by BMP9. When ERK1/2 kinase was silenced by RNA interference, BMP9-activated Smad pathway was further enhanced. Moreover, ALP activity, calcium deposition and in invo ectopic bone formation were accordingly increased along with knockdown of ERK1/2 kinase. Taken together, those results intensively suggested that BMP9 can activate ERK1/2 kinase, and inhibition of ERK1/2 kinase can enhance BMP9-induced osteogenic differentiation of mesenchymal stem cells. ERK1/2 are highly capable of negatively regulate BMP9-induced osteoblastic differentiation of mesenchymal stem cells.
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综述与专论
研究报告
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