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<p>Circular RNA (<i>circRNA</i>) is a unique closed ring structure of noncoding RNA. Although many human diseases have been confirmed to be inextricably linked with <i>circRNAs</i>, whether <i>circRNAs</i> have a potential regulatory function in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) remains to be further elucidated. In a previous study by our team, all the differentially expressed <i>circRNAs</i> and messenger RNAs (<i>mRNAs</i>) involved in the osteogenic differentiation of BMMSCs were identified via high-throughput sequencing, and a competing endogenous RNA (<i>ceRNA</i>) regulatory network was constructed via bioinformatics analysis. The <i>circRNA_1809/miR-370-3p/Kitlg</i> axis may be involved in regulating the osteogenic differentiation of BMMSCs. In this study, gene knockdown/overexpression, small interfering RNA (siRNA) transfection and mimic/inhibitor treatment were used to evaluate the regulatory effects of <i>circRNA_1809</i> on the <i>miR-370-3p</i>/<i>Kitlg</i> pathway and the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMMSCs) in vitro. The results revealed that <i>circRNA_1809</i> was upregulated and that <i>miR-370-3p</i> was downregulated during the osteogenic differentiation of rBMMSCs. The low expression of <i>circRNA_1809</i> significantly downregulated the expression of <i>Kitlg</i> and decreased the protein expression of ALP and RUNX2. The expression of <i>miR-370-3p</i> was negatively correlated with the expression of <i>Kitlg</i> in rBMMSCs and the ability to undergo osteogenic differentiation. In addition, a dual-luciferase assay confirmed the binding of <i>miR-370-3p</i> and <i>circRNA_1809</i>, and <i>si-circRNA_1809</i> + <i>miR-370-3p</i> inhibitor cotransfection reversed some of the downregulation of <i>Kitlg</i> induced by <i>si-circRNA_1809</i>, whereas <i>si-circRNA_1809</i> + <i>miR-370-3p</i> mimic increased the downregulation of <i>Kitlg</i>. Therefore, <i>circRNA_1809</i> may promote the expression of <i>Kitlg</i> by regulating <i>miR-370-3p</i> and subsequently promote the osteogenic differentiation of rBMMSCs.</p>

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CircRNA_1809 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells through miR-370-3p

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月6日

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  • Lei Zhang,
  • Yidan Xu,
  • Ningning Liu,
  • Mengjie Xu,
  • Refeina Tuerxun,
  • Mireyeti Shahatibieke,
  • Yuan Yao

摘要

Circular RNA (circRNA) is a unique closed ring structure of noncoding RNA. Although many human diseases have been confirmed to be inextricably linked with circRNAs, whether circRNAs have a potential regulatory function in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) remains to be further elucidated. In a previous study by our team, all the differentially expressed circRNAs and messenger RNAs (mRNAs) involved in the osteogenic differentiation of BMMSCs were identified via high-throughput sequencing, and a competing endogenous RNA (ceRNA) regulatory network was constructed via bioinformatics analysis. The circRNA_1809/miR-370-3p/Kitlg axis may be involved in regulating the osteogenic differentiation of BMMSCs. In this study, gene knockdown/overexpression, small interfering RNA (siRNA) transfection and mimic/inhibitor treatment were used to evaluate the regulatory effects of circRNA_1809 on the miR-370-3p/Kitlg pathway and the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMMSCs) in vitro. The results revealed that circRNA_1809 was upregulated and that miR-370-3p was downregulated during the osteogenic differentiation of rBMMSCs. The low expression of circRNA_1809 significantly downregulated the expression of Kitlg and decreased the protein expression of ALP and RUNX2. The expression of miR-370-3p was negatively correlated with the expression of Kitlg in rBMMSCs and the ability to undergo osteogenic differentiation. In addition, a dual-luciferase assay confirmed the binding of miR-370-3p and circRNA_1809, and si-circRNA_1809 + miR-370-3p inhibitor cotransfection reversed some of the downregulation of Kitlg induced by si-circRNA_1809, whereas si-circRNA_1809 + miR-370-3p mimic increased the downregulation of Kitlg. Therefore, circRNA_1809 may promote the expression of Kitlg by regulating miR-370-3p and subsequently promote the osteogenic differentiation of rBMMSCs.