Effects of a miR-31, Runx2, and Satb2 Regulatory Loop on the Osteogenic Differentiation of Bone Mesenchymal Stem Cells
Effects of a miR-31, Runx2, and Satb2 Regulatory Loop on the Osteogenic Differentiation of Bone Mesenchymal Stem Cells
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miR-31、Runx2 和 Satb2 调节环对骨间充质干细胞成骨分化的影响
DOI：
10.1089/scd.2012.0686
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发表时间：
2013-08-01
影响因子：
4
通讯作者：
Fan, Xianqun
中科院分区：
文献类型：
--
作者：
Deng, Yuan;Wu, Si;Fan, Xianqun
最近，一组miRNA，包括miR-31，被报道在成骨诱导过程中通过miR微阵列分析下调。目前尚不清楚miR-31表达的变化如何与骨转录因子合作激活调节骨髓间充质干细胞（BMSC）分化的生物学途径。在这里，使用miR-31的模拟物和抑制剂、用于敲低Runx 2的小干扰RNA和用于过表达Runx 2的质粒来研究miR-31、Runx 2和Satb 2对BMSC的成骨分化的影响。我们的研究结果表明，miR-31的表达在BMSC培养的分化过程中进行性下降。抑制miR-31显著增加BMSC培养物中碱性磷酸酶活性和矿化。此外，miR-31降低了Satb 2蛋白的水平，而不显著影响Satb 2 mRNA水平，Runx 2直接抑制miR-31的表达。miR-31的过表达显著降低了成骨转录因子OPN、BSP、OSX和OCN的表达，但不降低Runx 2的表达。此外，在增殖培养基中培养的BMSCs中miR-31的高表达抑制了Satb 2蛋白水平，这可能有助于维持BMSCs处于未分化状态。总之，我们的研究结果表明，Runx 2，Satb 2和miR-31的调节机制可能在诱导BMSC成骨分化中发挥重要作用。这项研究的结果为我们提供了一个更好的了解的分子机制，管理BMSC的命运。
Recently, a cohort of miRNAs, including miR-31, was reported to be downregulated during osteogenic induction by miR microarray analysis. It remains unclear how changes in miR-31 expression collaborate with bone transcription factors to activate the biological pathways that regulate the differentiation of bone mesenchymal stem cells (BMSCs). Here the effects of miR-31, Runx2, and Satb2 on the osteogenic differentiation of BMSCs were investigated using mimics and inhibitors of miR-31, small interfering RNA for knockdown of Runx2 and plasmids for overexpression of Runx2. Our results showed that miR-31 expression decreased progressively in BMSC cultures during differentiation. Inhibition of miR-31 dramatically increased the alkaline phosphatase activity and mineralization in BMSC cultures. Additionally, miR-31 diminished the levels of the Satb2 protein without significantly affecting Satb2 mRNA levels, and Runx2 directly repressed miR-31 expression. Overexpression of miR-31 significantly reduced expression of the osteogenic transcription factors OPN, BSP, OSX, and OCN, but not Runx2. Furthermore, the high expression of miR-31 in BMSCs cultured in the proliferation medium repressed Satb2 protein levels, which may contribute to the maintenance of BMSCs in an undifferentiated state. In conclusion, our results suggest that a Runx2, Satb2, and miR-31 regulatory mechanism may play an important role in inducing BMSC osteogenic differentiation. The results of this study provide us with a better understanding of the molecular mechanisms that govern the BMSC fate.