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

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

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

Hairui Yuan et al. J Cell Physiol. 2021 Mar.

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.

Keywords: NFIA; Wnt/β-catenin signaling; miR-142a-5p; osteoblast differentiation.

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