The circ_0054633/miR-590-3p/RUNX2 positive feedback loop promotes the osteogenic differentiation of BMSCs.

IF 7.1 2区医学 Q1 CELL & TISSUE ENGINEERING

Stem Cell Research & Therapy Pub Date : 2025-07-01 DOI:10.1186/s13287-025-04450-y

Lingxiao Wang, Yang Liu, Zhanqiu Diao, Yishu Huang, Haoqing Yang, Yue Zhang, Bowen Zhou, Zhenhua Gao, Zhaochen Shan, Jun Li, Zhipeng Fan

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引用次数: 0

Abstract

Background: Mandibular bone marrow stem cells (BMSCs) from patients with type 2 diabetes mellitus (T2DM) have poor osteogenic differentiation capacity. Elucidating the molecular mechanisms by which circular RNAs (circRNAs) play specific roles in T2DM will reveal new diagnostic biomarkers and therapeutic targets.

Methods: BMSCs with different circ_0054633 expression levels were generated. Furthermore, alkaline phosphatase (ALP) activity, alizarin red staining (ARS), and transplantation of HA/tricalcium phosphate into BMSCs were performed to detect the osteogenic effects of different levels of circ_0054633 expression in BMSCs in vivo and in vitro.

Results: In this study, we identified 80 differentially expressed circRNAs in jawbone-derived BMSCs from patients with T2DM. Notably, significant downregulation of circ_0054633 promoted the osteogenic differentiation of these cells in vitro and in vivo. Mechanistically, circ_0054633 acts as a miRNA sponge; specifically, it actively regulates the expression of RUNX2 by sponging miR-590-3p and thus promoting the osteogenic differentiation of the BMSCs. In addition, we found that circ_0054633 was a direct transcriptional target of RUNX2. RUNX2 overexpression activated the circ_0054633 promoter and promoted the generation of nuclear circ_0054633, whereas RUNX2 knockdown abrogated the osteogenic role of circ_0054633 and formed a circ_005463/miR-590-3p/RUNX2 positive feedback loop.

Conclusions: Our results suggest that the circ_0054633/miR-590-3p/RUNX2 positive feedback loop promotes the osteogenic differentiation of BMSCs and is expected to be a potential biomarker and therapeutic target for bone regeneration in T2DM.

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circ_0054633/miR-590-3p/RUNX2正反馈回路促进BMSCs成骨分化。

背景：2型糖尿病（T2DM）患者的下颌骨髓干细胞（BMSCs）成骨分化能力较差。阐明环状rna （circRNAs）在T2DM中发挥特定作用的分子机制将揭示新的诊断生物标志物和治疗靶点。方法：制备不同circ_0054633表达水平的骨髓间充质干细胞。此外，通过碱性磷酸酶（ALP）活性、茜素红染色（ARS）和HA/磷酸三钙移植骨髓间充质干细胞，检测不同水平circ_0054633在骨髓间充质干细胞体内和体外表达的成骨作用。结果：在这项研究中，我们在T2DM患者颌骨来源的骨髓间质干细胞中鉴定了80种差异表达的环状rna。值得注意的是，circ_0054633的显著下调促进了这些细胞在体外和体内的成骨分化。从机制上讲，circ_0054633充当miRNA海绵；具体来说，它通过海绵化miR-590-3p积极调节RUNX2的表达，从而促进骨髓间充质干细胞的成骨分化。此外，我们发现circ_0054633是RUNX2的直接转录靶点。RUNX2过表达激活了circ_0054633启动子，促进了核circ_0054633的产生，而RUNX2敲低则取消了circ_0054633的成骨作用，形成了circ_005463/miR-590-3p/RUNX2的正反馈回路。结论：我们的研究结果表明circ_0054633/miR-590-3p/RUNX2正反馈回路促进BMSCs的成骨分化，有望成为T2DM骨再生的潜在生物标志物和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL

CiteScore

13.20

自引率

8.00%

发文量

525

审稿时长

1 months

期刊介绍： Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.