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miR-142a-5p 通过靶向核因子 IA 促进成骨细胞分化。

miR-142a-5p promoted osteoblast differentiation via targeting nuclear factor IA.

机构信息

NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.

出版信息

J Cell Physiol. 2021 Mar;236(3):1810-1821. doi: 10.1002/jcp.29963. Epub 2020 Jul 23.

Abstract

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.

摘要

miR-142a-5p 在多种生物过程和疾病中发挥着关键作用,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探索。在这项研究中,我们的结果表明 miR-142a-5p 在小鼠骨组织中高度表达,并在成骨前体细胞 MC3T3-E1 细胞的成骨过程中增加。使用 miR-142a-5p agomir 补充 miR-142a-5p 的活性可促进基质细胞系 ST2 和前成骨细胞系 MC3T3-E1 的成骨分化。相反,miR-142a-5p antagomir,一种内源性 miR-142a-5p 的抑制剂,可减少 ST2 和 MC3T3-E1 细胞中的成骨分化。核因子 IA(NFIA),一种特定于核的转录因子,被证明是 miR-142a-5p 的直接靶标。NFIA 的过表达抑制了 ST2 细胞中 miR-142a-5p 介导的成骨分化。此外,机制探索表明 Wnt/β-catenin 信号通路在成骨分化过程中转录调控 miR-142a-5p 的表达。β-catenin 结合到 miR-142 启动子中的 T 细胞因子/淋巴增强因子结合基序,正向调节其转录活性。我们的研究结果表明,miR-142a-5p 通过靶向 NFIA 促进成骨细胞分化。

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