TITLE:
The Role of Ferroptosis and the Associated Gene CDKN1A in the Progression of Osteoarthritis
AUTHORS:
Jinyou Nie, Fei Dou, Taoxian Wang, Rongxin Meng, Zeyu Hou, Dinggui Lu
KEYWORDS:
Osteoarthritis, Ferroptosis, CDKN1A, Bioinformatics, Mendelian Randomization
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.4,
April
29,
2026
ABSTRACT: Objective: To investigate the role and diagnostic value of ferroptosis-related genes, especially Cyclin-Dependent Kinase Inhibitor 1A (CDKN1A), in osteoarthritis (OA), and to assess the causal relationship between iron metabolism and the disease. Methods: OA-related differentially expressed genes (DEGs) from the GEO database were intersected with ferroptosis-related genes from FerrDb V3. Functional insights were obtained via GO/KEGG enrichment and PPI network analysis. Diagnostic value was evaluated using ROC curves. Mendelian randomization assessed causality using ferritin and TSAT as exposures and OA as the outcome. In vitro, an inflammatory model was established by stimulating chondrocytes with IL-1β with or without a ferroptosis inhibitor, and CDKN1A and Col2 expression were detected. Results: Nine ferroptosis-related DEGs were identified. Enrichment analysis implicated these genes in long-chain fatty acid metabolism. ROC curve analysis showed high diagnostic efficacy for CDKN1A. Mendelian randomization revealed a significant positive causal association between increased transferrin saturation and OA risk. In vitro experiments demonstrated that inflammatory stimulation significantly reduced CDKN1A and Col2 expression in chondrocytes, an effect partially reversed by ferroptosis inhibitor intervention. Conclusion: The ferroptosis-related gene CDKN1A is downregulated in OA cartilage and may contribute to chondrocyte injury, potentially through ferroptosis‑related pathways. Iron metabolism disorders are causally linked to OA.