miR-27 promotes osteoblast differentiation by modulating Wnt signaling

miR-27 promotes osteoblast differentiation by modulating Wnt signaling
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DOI:
10.1016/j.bbrc.2010.08.031
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发表时间:
2010-11-12
影响因子:
3.1
通讯作者:
Xu, Zhengyu
Xu, Zhengyu
中科院分区:
生物学4区
文献类型:
--
作者:
Wang, Tao;Xu, Zhengyu

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典型的Wnt信号传导对于人类间充质干细胞分化为成骨细胞特别重要。microRNA(miRNAs)在调节细胞分化中也起着重要作用。然而,miRNAs在成骨细胞分化中的作用仍然知之甚少。我们发现miR-27在hFOB1.19细胞分化过程中表达增加。此外,miR-27的异位表达促进了hFOB 1. 19细胞的分化,而其抑制作用足以抑制细胞分化。Western blot分析显示miR-27的表达水平与Wnt信号通路中的关键蛋白p-catenin的表达水平呈正相关。此外,我们证实了miR-27直接靶向并抑制腺瘤性息肉病结肠(APC)基因表达,并通过β-连环蛋白的积累激活Wnt信号传导。这项研究表明,miR-27是成骨细胞分化的重要介质,从而为开发预防或治疗成骨疾病的药物提供了新的靶点。(C)2010年由Elsevier Inc.出版
Canonical Wnt signaling is particularly important for differentiation of human mesenchymal stem cells into osteoblast. MicroRNAs (miRNAs) also play an essential role in regulating cell differentiation. However, the role of miRNAs in osteoblast differentiation remains poorly understood. Here we found that the expression of miR-27 was increased during hFOB1.19 cells differentiation. Moreover, ectopic expression of miR-27 promoted hFOB1.19 cells differentiation, whereas its repression was sufficient to inhibit cell differentiation. Western blot analysis showed that the expression level of miR-27 was positively correlated with that of p-catenin, a key protein in Wnt signaling. Further, we verified that miR-27 directly targeted and inhibited adenomatous polyposis coli (APC) gene expression, and activated Wnt signaling through accumulation of p-catenin. This study suggests miR-27 is an important mediator of osteoblast differentiation, thus offering a new target for the development of preventive or therapeutic agents against osteogenic disorders. (C) 2010 Published by Elsevier Inc.