Increased Expression of miR-7a-5p and miR-592 during Expansion of Rat Dental Pulp Stem Cells and Their Implication in Osteogenic Differentiation.
Increased Expression of miR-7a-5p and miR-592 during Expansion of Rat Dental Pulp Stem Cells and Their Implication in Osteogenic Differentiation.
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DOI：
10.1159/000519600
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yao S
中科院分区：
文献类型：
--
作者：
Rong W;Rome C;Yao S
牙髓干细胞(DPSCs)具有很强的成骨分化潜能，在再生医学中具有广阔的应用前景。然而，在体外扩增过程中，这种分化能力逐渐下降。MicroRNAs(MiRNAs)在调节干细胞分化中发挥重要作用。本研究旨在(A)确定miR-7a-5p和miR-592是否参与维持和调节DPSCs的成骨分化，以及(B)探讨其潜在的调控途径。我们发现在大鼠DPSCs(RDPSCs)扩增过程中miR-7a-5p和miR-592表达显著上调。这些miRNAs的过表达抑制了rDPSCs的成骨/成牙分化，表现为钙沉积和成骨/成牙基因表达。RT-qPCR结果表明，miR-592可以下调热休克蛋白B8的表达，该蛋白在rDPSCs扩增过程中表达降低。此外，RNA-seq和生物信息学分析发现miR-7a-5p和miR-592在调控成骨分化中有重要的信号通路，包括肿瘤坏死因子、MAPK和PI3K-Akt通路。我们的结论是，上调miR-7a-5p和miR-592可抑制rDPSC在体外扩增过程中的成骨分化，可能是通过肿瘤坏死因子、MAPK和PI3K-Akt途径实现的。这一结果可能为应用miR-7a-5p和miR-592维持干细胞的成骨分化潜能用于骨再生和骨相关疾病的治疗提供参考。
Dental pulp stem cells (DPSCs) possess strong osteogenic differentiation potential and are promising cell sources in regenerative medicine. However, such differentiation capacity progressively declines during their in vitro expansion. MicroRNAs (miRNAs) play important roles in modulating stem cell differentiation. This study aimed (a) to determine if miR-7a-5p and miR-592 are involved in maintaining and regulating osteogenic differentiation of DPSCs, and (b) to explore their potential regulatory pathways. We found that the expression of miR-7a-5p and miR-592 was significantly upregulated during the expansion of rat DPSCs (rDPSCs). Overexpression of these miRNAs inhibited the osteogenic/odontogenic differentiation of rDPSCs, as evidenced by calcium deposition and osteogenic/odontogenic gene expression. RT-qPCR determined that miR-592 could downregulate heat shock protein B8, whose expression is reduced during the expansion of rDPSCs. Furthermore, RNA-seq and bioinformatics analysis identified significant signaling pathways of miR-7a-5p and miR-592 in regulating osteogenic differentiation, including TNF, MAPK, and PI3K-Akt pathways. We conclude that upregulating miR-7a-5p and miR-592 suppresses the osteogenic differentiation of rDPSCs during their in vitro expansion, likely via TNF, MAPK and PI3K-Akt pathways. The results may shed light on application of miR-7a-5p and miR-592 for maintaining osteo-differentiation potential in stem cells for bone regeneration and bone-related disease treatment.
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