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Background <p>Nonunion occurs in about 10% of fracture cases, which leads to secondary surgical injury and economic burden for patients.</p> Purpose <p>Our study aimed to confirm the effects of miR-376a-3p/<i>WWTR1</i> on fracture healing.</p> Methods <p>Through bioinformatics analysis, we found that miR-376a-3p was highly expressed in patients with fracture nonunion. We confirmed the interaction of miR-376a-3p and <i>WWTR1</i> by using RT-qPCR, RNA immunoprecipitation, and Dual-Luciferase assay. Rescue experiment was used to explore the effects of miR-376a-3p/<i>WWTR1</i> on human bone marrow mesenchymal stem cells (hBMSCs) differentiation into osteoblasts.</p> Results <p>We confirmed that miR-376a-3p was up-regulated in fracture nonunion patients by a retrospective study of clinical data of fracture patients. In vitro experiments showed that inhibiting the miR-376a-3p would increase the expression of <i>WWTR1</i>. It was found in the induction of the hBMSCs differentiation assay that inhibition of miR-376a-3p or overexpression of <i>WWTR1</i> could increase the level of <i>ALP, Runx2,</i> and <i>OSX</i> in cell supernatant, which reflected the increased differentiation of hBMSCs into osteoblasts. And rescue experiment confirmed that miR-376a-3p inhibits differentiation of hBMSCs through targeted regulating <i>WWTR1</i>.</p> Conclusion <p>We revealed the regulatory role of miR-376a-3p/<i>WWTR1</i> in fracture nonunion by inhibiting osteogenic induction, which provides the possibility that miR-376a-3p may be a new underlying target for fracture nonunion prediction and therapy.</p>

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MiR-376a-3p inhibits bone repair by regulating osteoblastic differentiation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月13日

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  • Jian Zhang,
  • Jinxiang Zhang,
  • Fangyuan Zhang,
  • Shaochun Jing,
  • Debing Yang

摘要

Background

Nonunion occurs in about 10% of fracture cases, which leads to secondary surgical injury and economic burden for patients.

Purpose

Our study aimed to confirm the effects of miR-376a-3p/WWTR1 on fracture healing.

Methods

Through bioinformatics analysis, we found that miR-376a-3p was highly expressed in patients with fracture nonunion. We confirmed the interaction of miR-376a-3p and WWTR1 by using RT-qPCR, RNA immunoprecipitation, and Dual-Luciferase assay. Rescue experiment was used to explore the effects of miR-376a-3p/WWTR1 on human bone marrow mesenchymal stem cells (hBMSCs) differentiation into osteoblasts.

Results

We confirmed that miR-376a-3p was up-regulated in fracture nonunion patients by a retrospective study of clinical data of fracture patients. In vitro experiments showed that inhibiting the miR-376a-3p would increase the expression of WWTR1. It was found in the induction of the hBMSCs differentiation assay that inhibition of miR-376a-3p or overexpression of WWTR1 could increase the level of ALP, Runx2, and OSX in cell supernatant, which reflected the increased differentiation of hBMSCs into osteoblasts. And rescue experiment confirmed that miR-376a-3p inhibits differentiation of hBMSCs through targeted regulating WWTR1.

Conclusion

We revealed the regulatory role of miR-376a-3p/WWTR1 in fracture nonunion by inhibiting osteogenic induction, which provides the possibility that miR-376a-3p may be a new underlying target for fracture nonunion prediction and therapy.