miR‐142a‐5p promoted osteoblast differentiation via targeting nuclear factor IA
miR‐142a‐5p promoted osteoblast differentiation via targeting nuclear factor IA
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DOI：
10.1002/jcp.29963
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发表时间：
2020-07
影响因子：
5.6
通讯作者：
Hairui Yuan;Mengyue Li;Xue Feng;Endong Zhu;Baoli Wang
中科院分区：
文献类型：
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作者：
Hairui Yuan;Mengyue Li;Xue Feng;Endong Zhu;Baoli Wang
MiR-142a-5p在多种生物学过程和疾病中发挥关键作用，如炎症和肿瘤发生。然而，miR-142a-5p是否以及如何促进成骨细胞分化仍有待研究。本研究结果表明，miR-142a-5p在小鼠骨组织中高表达，并在成骨前细胞MC3T3-E1中高表达。补充miR-142a-5p活性可促进基质细胞系ST2和成骨前细胞系MC3T3-E1的成骨分化。相反，内源性miR-142a-5p的抑制剂miR-142a-5p antagomir可以减少ST2和MC3T3-E1细胞的成骨细胞分化。核因子IA(NFIA)是一种位点特异性转录因子，被证明是miR-142a-5p直接靶向的转录因子。NFIA过表达抑制了miR-142a-5p介导的ST2细胞成骨分化。进一步的机制探索表明，在成骨分化过程中，Wnt/β-catenin信号转录调控miR-142a-5p的表达。β-catenin与miR142启动子内的T细胞因子/淋巴增强因子结合基序结合，正向调节其转录活性。我们的研究结果提示miR-142a-5p通过靶向NFIA促进成骨细胞分化。
miR‐142a‐5p plays critical roles in multiple biological processes and diseases, such as inflammation and tumorigenesis. However, it remains to be explored if and how miR‐142a‐5p contributes to osteoblast differentiation. In this study, our results showed that miR‐142a‐5p was highly expressed in bone tissue of mice and increased during osteogenesis in preosteoblast MC3T3‐E1 cells. Supplementing miR‐142a‐5p activity using miR‐142a‐5p agomir promoted osteogenic differentiation in stromal cell line ST2 and preosteoblastic line MC3T3‐E1. Conversely, miR‐142a‐5p antagomir, an inhibitor of endogenous miR‐142a‐5p, could reduce osteoblast differentiation in ST2 and MC3T3‐E1 cells. Nuclear factor IA (NFIA), a site‐specific transcriptional factor, was demonstrated to be directly targeted by miR‐142a‐5p. Overexpression of NFIA inhibited miR‐142a‐5p‐mediated osteoblast differentiation in ST2 cells. Furthermore, mechanism explorations revealed that Wnt/β‐catenin signaling transcriptionally regulated the expression of miR‐142a‐5p during osteogenic differentiation. β‐catenin binds to the T‐cell factor/lymphoid enhancer factor binding motif within the promoter of miR‐142 and positively regulates its transcriptional activity. Our findings suggested that miR‐142a‐5p promoted osteoblast differentiation via targeting NFIA.