PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells
PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells
复制标题
DOI：
10.1016/j.bbrc.2014.04.091
复制
发表时间：
2014-06-06
影响因子：
3.1
通讯作者：
Pan, Xian-ming
中科院分区：
文献类型：
--
作者：
Qu, Bo;Xia, Xun;Pan, Xian-ming
分化特异性microrna可能在MSC分化中发挥关键作用，它们可以被PDGF信号改变。我们提出PDGF通过调节microRNA的表达来调节MSC分化。因此，我们研究了PDGF处理是否会改变MSCs中mirna的表达谱。此外，我们评估了诱导成骨分化后MSCs的成骨细胞表型。我们发现PDGF处理显著抑制MSCs的成骨分化，miR-138基因转录受PDGF信号传导控制。我们的研究结果证实，miR-138抑制MSCs的成骨分化，并抑制FAK、ERK1/2和Runx2的磷酸化。此外，我们的研究清楚地表明，miR-138下调Runx2对于pdgf介导的MSCs成骨分化抑制至关重要。这些发现表明，通过抗miR-138或通过过表达miR-138靶序列（miRNA海绵）来抑制MSCs中miR-138的功能，可能代表了一种潜在的治疗策略，用于治疗由PDGF通路激活引起的骨稳态紊乱。(C) 2014爱思唯尔公司版权所有。
Differentiation-specific microRNAs may play a critical role in MSC differentiation, and they can be altered by PDGF signaling. We propose that PDGF modulates MSC differentiation by regulating microRNA expression. Therefore, we investigated whether PDGF treatment could alter the expression profile of miRNAs in MSCs. Furthermore, we assessed the osteoblast phenotype of MSCs after inducing osteogenic differentiation. We found that PDGF treatment significantly inhibits the osteogenic differentiation of MSCs and that miR-138 gene transcription is controlled by PDGF signaling. Our results confirm that miR-138 inhibits the osteogenic differentiation of MSCs and suppresses the phosphorylation of FAK, ERK1/2, and Runx2. Furthermore, our study clearly demonstrates that downregulation of Runx2 by miR-138 is critical for the PDGF-mediated inhibition of osteogenic differentiation of MSCs. These findings indicate that inhibition of miR-138 function in MSCs, either by treatment with anti-miR-138 or by overexpression of the miR-138 target sequence (miRNA sponge), could represent a potential therapeutic strategy for the treatment of bone homeostasis disorders caused by activation of the PDGF pathway. (C) 2014 Elsevier Inc. All rights reserved.