YTHDF3-associated m6A regulation and cuproptosis-related gene expression in steroid-induced osteonecrosis of the femoral head

IF 2.2 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2025-08-29 DOI:10.1007/s10735-025-10544-x

Yong Cui, Aikeremujiang Alken, Wu Wang, Tao Huang, Zhongwei Li

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引用次数: 0

Abstract

This study aims to explore the role of N6-methyladenosine (m6A) RNA modification in regulating Cuproptosis in steroid-induced osteonecrosis of the femoral head (SONFH), providing insights into its underlying mechanisms and therapeutic targets. Gene expression profiles from both human (GSE123568; 30 SONFH patients and 10 controls) and rat femoral head samples (GSE26316; 3 SONFH and 3 controls) were analyzed to identify differentially expressed genes (DEGs) and enriched pathways. In a matched case-control study, femoral head tissues from SONFH patients and non-SONFH controls were collected. The expression of YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and dihydrolipoamide dehydrogenase (DLD) was measured using qRT-PCR and Western blotting. Functional validation was performed in human bone marrow mesenchymal stem cells (BMSCs) via siRNA-mediated knockdown of YTHDF3 and treatment with elesclomol, a cuproptosis inducer. In the GSE26316 and GSE123568 datasets, we identified 708 common DEGs. Cuproptosis were activated in SONFH. The expression levels of YTHDF3 and DLD were elevated in SONFH tissues. Knockdown of YTHDF3 reduced the DLD expression and mitigated the inhibitory effects of elesclomol on BMSC proliferation and osteogenesis. YTHDF3 may contribute to SONFH progression by regulating DLD expression and cuproptosis, offering a potential important molecular target for novel therapeutic strategies.

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激素性股骨头坏死中ythdf3相关m6A的调控和铜中毒相关基因的表达

本研究旨在探讨n6 -甲基腺苷（m6A） RNA修饰在激素性股骨头骨坏死（SONFH）中cuprotosis的调控作用，揭示其潜在机制和治疗靶点。分析了人（GSE123568, 30例SONFH患者和10例对照）和大鼠股骨头样本（GSE26316, 3例SONFH和3例对照）的基因表达谱，以鉴定差异表达基因（deg）和富集途径。在一项匹配的病例对照研究中，收集了SONFH患者和非SONFH对照组的股骨头组织。采用qRT-PCR和Western blotting检测YTH n6 -甲基腺苷RNA结合蛋白3 （YTHDF3）和二氢脂酰胺脱氢酶（DLD）的表达。在人骨髓间充质干细胞（BMSCs）中，通过sirna介导的YTHDF3敲低和使用铜生长诱导性药物埃来氯莫尔（elesclomol）进行功能验证。在GSE26316和GSE123568数据集中，我们确定了708个共同的deg。在SONFH中cuprotosis被激活。YTHDF3和DLD在SONFH组织中的表达水平升高。下调YTHDF3可降低DLD的表达，减轻依来洛莫尔对BMSC增殖和成骨的抑制作用。YTHDF3可能通过调节DLD表达和cuprotosis来促进SONFH的进展，为新的治疗策略提供了一个潜在的重要分子靶点。

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来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.