Fig. 2: Post-discectomy ferroptosis of NPCs promotes IDD. | Nature Communications

Fig. 2: Post-discectomy ferroptosis of NPCs promotes IDD.

From: Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes

Fig. 2

a–f Analysis of RNA sequencing data from human intervertebral discs (GSE70362) obtained from the Gene Expression Omnibus (GEO) database. a Principal Component Analysis (PCA) of the reorganized samples from GSE70362. b Volcano plot illustrating the DEGs between the two groups. The significant DEGs were filtered with thresholds of a |log2(fold change, FC)| > 2 and P value < 0.05 using the R package DESeq2. c Heatmap showing significant DEGs between the control and degenerative NPs. d Gene Ontology (GO) analysis of the RNA-seq results. e Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the RNA-seq results. f Gene Set Enrichment Analysis (GSEA) of gene sets related to ferroptosis for the control and degenerative NPs. g–j Evaluation of ferroptosis-related markers in IVDs of rats at various time points post-discectomy. g Diagram depicting the discectomy procedure in rats. h qRT-PCR analysis of typical ferroptosis-related markers in the IVDs post-discectomy (n = 6 independent rats). The expression of ACSL4 and GPX4 (i) and associated quantitative analysis (j) in IVD after discectomy (n = 6 independent rats). k–l Malondialdehyde (MDA) and ferrous ion levels in the IVD at different time points post-discectomy (n = 5 independent rats). The expression of COL2 and MMP13 (m) and associated quantitative analysis (n) in IVD after discectomy (n = 6 independent rats). In panels (d–f) the gene enrichment analysis was performed using the hypergeometric test with multiple testing correction. Comparisons were performed by two-tailed Student’s t test in panels (h, j, k, l and n). Data are presented as means ± SD. DEGs Differentially Expressed Genes, IVD intervertebral disc, IDD intervertebral disc degeneration, ACSL4 acyl-CoA synthetase long chain family member 4, GPX4 glutathione peroxidase 4, COL2 Collagen II, MMP13 matrix metallopeptidase 13, ZVAD-FMK a pan caspase inhibitor, Fer-1 ferrostatin-1. Schematic illustrations were generated using BioRender (Wang, V., 2025; accessible at: https://BioRender.com/i62o243). Source data are provided as a Source Data file.

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