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低频正弦电磁场通过调节miR-34b-5p/STAC2促进大鼠骨髓间充质干细胞的成骨分化。

Low frequency sinusoidal electromagnetic fields promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells by modulating miR-34b-5p/STAC2.

作者信息

Fang Xuan, Liu Changyu, Wei Kang, Shu Zixing, Zou Yi, Zhang Zihao, Ding Qing, Jing Shaoze, Li Weigang, Wang Tianqi, Li Hao, Wu Hua, Liu Chaoxu, Ma Tian

机构信息

Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Division of Cardiovascular Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Commun Biol. 2024 Sep 16;7(1):1156. doi: 10.1038/s42003-024-06866-3.

Abstract

Electromagnetic fields (EMFs) have emerged as an effective treatment for osteoporosis. However, the specific mechanism underlying their therapeutic efficacy remains controversial. Herein, we confirm the pro-osteogenic effects of 15 Hz and 0.4-1 mT low-frequency sinusoidal EMFs (SEMFs) on rat bone marrow mesenchymal stem cells (BMSCs). Subsequent miRNA sequencing reveal that miR-34b-5p is downregulated in both the 0.4 mT and 1 mT SEMFs-stimulated groups. To clarify the role of miR-34b-5p in osteogenesis, BMSCs are transfected separately with miR-34b-5p mimic and inhibitor. The results indicate that miR-34b-5p mimic transfection suppress osteogenic differentiation, whereas inhibition of miR-34b-5p promote osteogenic differentiation of BMSCs. In vivo assessments using microcomputed tomography, H&E staining, and Masson staining show that miR-34b-5p inhibitor injections alleviate bone mass loss and trabecular microstructure deterioration in ovariectomy (OVX) rats. Further validation demonstrates that miR-34b-5p exerts its effects by regulating STAC2 expression. Modulating the miR-34b-5p/STAC2 axis attenuate the pro-osteogenic effects of low-frequency SEMFs on BMSCs. These studies indicate that the pro-osteogenic effect of SEMFs is partly due to the regulation of the miR-34b-5p/STAC2 pathway, which provides a potential therapeutic candidate for osteoporosis.

摘要

电磁场(EMFs)已成为治疗骨质疏松症的一种有效方法。然而,其治疗效果背后的具体机制仍存在争议。在此,我们证实了15Hz和0.4 - 1mT低频正弦电磁场(SEMFs)对大鼠骨髓间充质干细胞(BMSCs)具有促骨生成作用。随后的miRNA测序显示,在0.4mT和1mT SEMFs刺激组中,miR - 34b - 5p均下调。为阐明miR - 34b - 5p在骨生成中的作用,分别用miR - 34b - 5p模拟物和抑制剂转染BMSCs。结果表明,转染miR - 34b - 5p模拟物会抑制成骨分化,而抑制miR - 34b - 5p则促进BMSCs的成骨分化。使用微型计算机断层扫描、苏木精 - 伊红染色和马松染色进行的体内评估表明,注射miR - 34b - 5p抑制剂可减轻去卵巢(OVX)大鼠的骨质流失和小梁微结构恶化。进一步验证表明,miR - 34b - 5p通过调节STAC2表达发挥其作用。调节miR - 34b - 5p/STAC2轴可减弱低频SEMFs对BMSCs的促骨生成作用。这些研究表明,SEMFs的促骨生成作用部分归因于对miR - 34b - 5p/STAC2途径的调节,这为骨质疏松症提供了一种潜在的治疗候选方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a79/11405519/7efdf674568e/42003_2024_6866_Fig1_HTML.jpg

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