| 陈磊,高明.铜死亡基因FDX1与骨关节炎软骨梯度退变的线粒体代谢相关性[J].济宁医学院学报,2026,49(5):436-441 |
| 铜死亡基因FDX1与骨关节炎软骨梯度退变的线粒体代谢相关性 |
| Correlation analysis of cuproptosis-related gene FDX1 with mitochondrialmetabolism in gradient cartilage degeneration of osteoarthritis |
| 投稿时间：2026-06-15 |
| DOI：10.3969/j.issn.1000-9760.2026.05.009 |
| 中文关键词: 骨关节炎 FDX1 铜死亡 线粒体 转录组分析 软骨退变 |
| 英文关键词: Osteoarthritis FDX1 Cuproptosis Mitochondria Transcriptome analysis Cartilage degeneration |
| 基金项目:济宁市重点研发计划(2025YXNS027) |
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| 中文摘要: |
| 目的 探讨铁氧还蛋白1（FDX1）相关的铜死亡通路在骨关节炎（OA）发生发展中的表达特征及潜在关联。方法 本研究基于美国国家生物技术信息中心（NCBI）基因表达综合数据库（GEO）GSE57218转录组数据集，纳入健康软骨、退变保留区软骨及OA病变软骨样本73例，其中退变保留区软骨和OA病变软骨来自同一批患者，为配对样本。通过差异表达分析筛选铜死亡核心基因在软骨退变不同阶段的表达特征；采用单样本基因集富集分析（ssGSEA）计算铜死亡通路富集评分，评估通路整体活性；通过基因集富集分析（GSEA）解析FDX1相关的线粒体能量代谢通路。结果 与健康软骨相比，退变保留区与OA病变软骨中FDX1、LIPT1、MTF1等铜死亡相关基因表达均显著下调；铜死亡通路活性在退变保留区即显著降低，并在病变阶段持续维持低水平。GSEA分析显示，FDX1表达水平与ATP合成、线粒体ATP合成等多条能量代谢通路呈显著负相关，FDX1低表达对应线粒体能量代谢通路异常激活。结论 本研究首次在OA梯度退变软骨中揭示FDX1相关铜死亡通路与线粒体代谢重编程的关联，为OA发病机制研究提供了新视角；FDX1有望成为OA的潜在候选生物标志物，靶向铜死亡通路也为该病的防治提供了新的研究方向。 |
| 英文摘要: |
| Objective To explore the expression characteristics and potential associations of the FDX1-related cuproptosis pathway in the initiation and progression of osteoarthritis.Methods Based on the NCBI Gene Expression Omnibus (GEO) GSE57218 dataset,73 samples were enrolled:healthy cartilage,preserved degenerative cartilage,and osteoarthritis (OA) lesioned cartilage,in which preserved degenerative and OA cartilage were paired samples from the same patients.Differential expression analysis was performed to characterize the expression patterns of core cuproptosis genes across different stages of cartilage degeneration.Single-sample gene set enrichment analysis (ssGSEA) was applied to calculate cuproptosis pathway enrichment scores for evaluating overall pathway activity.Gene set enrichment analysis (GSEA) was used to identify mitochondrial energy metabolism pathways associated with FDX1.Results Compared with healthy cartilage,the expression of cuproptosis-related genes including FDX1,LIPT1 and MTF1 was significantly downregulated in preserved degenerative cartilage and osteoarthritic lesional cartilage.Cuproptosis pathway activity decreased significantly at the preserved degenerative stage and remained low in the lesional stage.GSEA demonstrated that FDX1 expression was significantly negatively correlated with multiple energy metabolism pathways such as ATP synthesis and mitochondrial ATP synthesis,suggesting that low FDX1 expression corresponded to aberrant activation of mitochondrial energy metabolism pathways.Conclusion This study identifies for the first time the association between the FDX1-related cuproptosis pathway and mitochondrial metabolic reprogramming in gradient degenerative OA cartilage,providing new insights into the pathogenesis of osteoarthritis.FDX1 may serve as a potential candidate biomarker for osteoarthritis,and targeting the cuproptosis pathway offers a new research direction for the prevention and treatment of this disease. |
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