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Objective <p>This study aimed to identify key mitochondria-related genes involved in the pathogenesis of osteoarthritis (OA).</p> Methods <p>Publicly available OA-related gene expression datasets were analyzed. Differential expression analysis, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), and machine learning were used to identify hub differentially expressed mitochondria-related genes (DE-MRGs) for constructing a molecular signature to predict OA risk. In addition, a nomogram, protein–protein interaction (PPI) network, gene set enrichment analysis (GSEA), and a competing endogenous RNA (ceRNA) network of signature DE-MRGs were generated to assess their predictive performance and regulatory mechanisms in OA. The expression of signature DE-MRGs was validated in interleukin (IL)-1β-treated chondrocytes, and the effects of <i>IMMT</i> knockdown on OA pathogenesis and mitochondrial dysfunction were investigated in vitro.</p> Results <p>A molecular signature comprising seven DE-MRGs (<i>IMMT</i>, <i>LONP1</i>, <i>TUFM</i>, <i>SOD2</i>, <i>CYCS</i>, <i>CAT</i>, and <i>DLD</i>) demonstrated high predictive performance for OA. The nomogram established using these genes also exhibited high predictive accuracy for OA risk. Furthermore, GSEA revealed that <i>IMMT</i> was implicated in pathways such as Notch signaling. A ceRNA network involving MEG3–miR-370-3p–<i>IMMT</i> was predicted. Quantitative PCR confirmed significant downregulation of <i>IMMT</i>, <i>TUFM</i>, <i>CAT</i>, and <i>DLD</i> in IL-1β-treated chondrocytes. Knockdown of <i>IMMT</i> promoted OA development and induced mitochondrial dysfunction in chondrocytes.</p> Conclusion <p>The identified DE-MRG signature holds significant potential for predicting OA. The downregulation of <i>IMMT</i> may contribute to OA pathogenesis by inducing mitochondrial dysfunction. These findings provide a foundation for developing more effective diagnostic and therapeutic strategies for OA.</p>

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IMMT downregulation promotes osteoarthritis development by inducing mitochondrial dysfunction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月8日

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  • Lvlin Yang,
  • Binyang Wang,
  • Qing Ma,
  • Junjie Wang,
  • Yinghao Cheng

摘要

Objective

This study aimed to identify key mitochondria-related genes involved in the pathogenesis of osteoarthritis (OA).

Methods

Publicly available OA-related gene expression datasets were analyzed. Differential expression analysis, immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), and machine learning were used to identify hub differentially expressed mitochondria-related genes (DE-MRGs) for constructing a molecular signature to predict OA risk. In addition, a nomogram, protein–protein interaction (PPI) network, gene set enrichment analysis (GSEA), and a competing endogenous RNA (ceRNA) network of signature DE-MRGs were generated to assess their predictive performance and regulatory mechanisms in OA. The expression of signature DE-MRGs was validated in interleukin (IL)-1β-treated chondrocytes, and the effects of IMMT knockdown on OA pathogenesis and mitochondrial dysfunction were investigated in vitro.

Results

A molecular signature comprising seven DE-MRGs (IMMT, LONP1, TUFM, SOD2, CYCS, CAT, and DLD) demonstrated high predictive performance for OA. The nomogram established using these genes also exhibited high predictive accuracy for OA risk. Furthermore, GSEA revealed that IMMT was implicated in pathways such as Notch signaling. A ceRNA network involving MEG3–miR-370-3p–IMMT was predicted. Quantitative PCR confirmed significant downregulation of IMMT, TUFM, CAT, and DLD in IL-1β-treated chondrocytes. Knockdown of IMMT promoted OA development and induced mitochondrial dysfunction in chondrocytes.

Conclusion

The identified DE-MRG signature holds significant potential for predicting OA. The downregulation of IMMT may contribute to OA pathogenesis by inducing mitochondrial dysfunction. These findings provide a foundation for developing more effective diagnostic and therapeutic strategies for OA.