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<p>Intervertebral disc degeneration (IVDD), characterized by lower back pain, is a prevalent chronic orthopedic disease imposing significant physical and economic burdens. However, the molecular mechanisms of IVDD remain insufficiently explored, hindering clinical guidance. This study aimed to identify key targets of IVDD via bioinformatics, providing new therapeutic directions. Gene expression profiles GSE34095 and GSE150408 were retrieved from public databases, and IVDD-related gene datasets were obtained from GeneCards and CTD. Protein-protein interaction (PPI) networks were constructed, followed by functional enrichment analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome Pathway Knowledgebase (Reactome), and WikiPathways. Key genes associated with the ferroptosis pathway were screened, and the effect of resveratrol on IVDD was validated via in vitro and in vivo experiments. Enrichment analyses identified ferroptosis as the major signaling pathway in IVDD. Six key genes (Glutathione Peroxidase 4 (GPX4), Transferrin receptor (TFRC/TFR1), Solute Carrier Family 7 Member 11 (SLC7A11/xCT), Hypoxia Inducible Factor 1 Subunit Alpha Gene (HIF1A), Interleukin-6 (IL6), and Interleukin-1 Beta (IL1B)) were selected. In vitro studies showed that resveratrol inhibited ferroptosis in nucleus pulposus cells (NPCs), while in vivo experiments in rats confirmed that resveratrol alleviated IVDD by regulating ferroptosis-related genes. Molecular docking validated the binding of resveratrol to these key targets. This study demonstrates that resveratrol delays IVDD progression by inhibiting ferroptosis in NPCs, providing a novel therapeutic strategy for clinical IVDD prevention and treatment.</p>

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A New Direction for Delaying Intervertebral Disc Degeneration: Resveratrol Inhibits Ferroptosis in Nucleus Pulposus Cells

  • 期刊论文

  • 发表日期：

    2025年9月2日

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  • Hong Wang,
  • Feilong Li,
  • Yongliang Mei,
  • Taotao Wu,
  • Liquan Wang,
  • Pandeng Hao,
  • Shenjing Ci,
  • Zongchao Liu

摘要

Intervertebral disc degeneration (IVDD), characterized by lower back pain, is a prevalent chronic orthopedic disease imposing significant physical and economic burdens. However, the molecular mechanisms of IVDD remain insufficiently explored, hindering clinical guidance. This study aimed to identify key targets of IVDD via bioinformatics, providing new therapeutic directions. Gene expression profiles GSE34095 and GSE150408 were retrieved from public databases, and IVDD-related gene datasets were obtained from GeneCards and CTD. Protein-protein interaction (PPI) networks were constructed, followed by functional enrichment analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome Pathway Knowledgebase (Reactome), and WikiPathways. Key genes associated with the ferroptosis pathway were screened, and the effect of resveratrol on IVDD was validated via in vitro and in vivo experiments. Enrichment analyses identified ferroptosis as the major signaling pathway in IVDD. Six key genes (Glutathione Peroxidase 4 (GPX4), Transferrin receptor (TFRC/TFR1), Solute Carrier Family 7 Member 11 (SLC7A11/xCT), Hypoxia Inducible Factor 1 Subunit Alpha Gene (HIF1A), Interleukin-6 (IL6), and Interleukin-1 Beta (IL1B)) were selected. In vitro studies showed that resveratrol inhibited ferroptosis in nucleus pulposus cells (NPCs), while in vivo experiments in rats confirmed that resveratrol alleviated IVDD by regulating ferroptosis-related genes. Molecular docking validated the binding of resveratrol to these key targets. This study demonstrates that resveratrol delays IVDD progression by inhibiting ferroptosis in NPCs, providing a novel therapeutic strategy for clinical IVDD prevention and treatment.