微小RNA-23通过靶向MEF2C介导的丝裂原活化蛋白激酶信号通路抑制人骨髓间充质干细胞的成骨分化。
MicroRNA-23 suppresses osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting the MEF2C-mediated MAPK signaling pathway.
作者信息
Jiang Kai, Teng Guo-Dong, Chen Yan-Qing
机构信息
Hand Surgery, 971th Hospital of PLA, Qingdao, Shandong, China.
出版信息
J Gene Med. 2020 Oct;22(10):e3216. doi: 10.1002/jgm.3216. Epub 2020 Jun 9.
BACKGROUND
The present study aimed to determine the role and mechanism of miR-23 with respect to regulating the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs).
MATERIALS
The expression of miR-23 and MEF2C was measured in osteoporosis (OP) patients and healthy controls by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The correlation between miR-23 and MEF2C was determined by the Pearson correlation coefficient. Moreover, bioinformatic analysis was performed using public databases. Target gene function and potential pathways were further examined. Then, we used a miR-23 mimic or inhibitor to further explore the potential mechanism of miR-23.
RESULTS
miR-23 is found to be up-regulated and MEF2C is down-regulated in OP patients compared to healthy controls. miR-23 had a negative correlation with MEF2C (r = -0.937, p = 0.001). Bioinformatic analysis revealed that a total of 664 overlapping target genes were found in the TargetScan (http://www.targetscan.org), miRDB (http://mirdb.org) and miRanda (http://www.microrna.org/microrna/home.do) databases. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that miR-23 may regulate the mitogan-activated protein kinase (MAPK) signaling pathway. miR-23 is down-regulated and MEF2C is significantly up-regulated in the osteogenic differentiation of hBMSCs. MEF2C was significantly up-regulated in the osteogenic differentiation of hBMSCs. Overexpression of miR-23 significantly down-regulated alkaline phosphatase (ALP) activity and calcium deposition, whereas the miR-23 inhibitor had the opposite effects. Moreover, overexpression of miR-23 significantly decreased osteoblast-related markers (Runx2, Osx, ALP and OCN). Further experiments confirmed that MEF2C is a direct target of miR-23. Moreover, the miR-23 mimic enhanced the expression of p-p38 but had no effect on p-JNK.
CONCLUSIONS
miR-23 decreases the osteogenic differentiation of hBMSCs through the MEF2C/MAPK signaling pathway.
背景
本研究旨在确定miR-23在调节人骨髓间充质干细胞（hBMSCs）成骨分化方面的作用和机制。
材料
采用定量逆转录聚合酶链反应（qRT-PCR）检测骨质疏松症（OP）患者和健康对照者中miR-23和MEF2C的表达。通过Pearson相关系数确定miR-23与MEF2C之间的相关性。此外，使用公共数据库进行生物信息学分析。进一步研究靶基因功能和潜在途径。然后，我们使用miR-23模拟物或抑制剂进一步探索miR-23的潜在机制。
结果
与健康对照相比，OP患者中miR-23上调而MEF2C下调。miR-23与MEF2C呈负相关（r = -0.937，p = 0.001）。生物信息学分析显示，在TargetScan（http://www.targetscan.org）、miRDB（http://mirdb.org）和miRanda（http://www.microrna.org/microrna/home.do）数据库中总共发现了664个重叠的靶基因。此外，京都基因与基因组百科全书（KEGG）通路分析表明，miR-23可能调节丝裂原活化蛋白激酶（MAPK）信号通路。在hBMSCs的成骨分化过程中，miR-23下调而MEF2C显著上调。MEF2C在hBMSCs的成骨分化过程中显著上调。miR-23的过表达显著下调碱性磷酸酶（ALP）活性和钙沉积量，而miR-23抑制剂则产生相反的效果。此外，miR-23的过表达显著降低成骨细胞相关标志物（Runx2、Osx、ALP和OCN）。进一步的实验证实MEF2C是miR-23的直接靶标。此外，miR-23模拟物增强了p-p38的表达，但对p-JNK没有影响。
结论
miR-23通过MEF2C/MAPK信号通路降低hBMSCs的成骨分化。
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