Identification and validation of key genes associated with nucleotide metabolism in osteoarthritis

Osteoarthritis (OA) is a prevalent degenerative joint disease with limited diagnostic and therapeutic options. Recent studies suggest that nucleotide metabolism (NM) plays a key role in OA progression. This study aimed to identify NM-related genes involved in OA and explore their potential mechanisms. Transcriptomic data from the GEO database were analyzed using differential expression and machine learning approaches. Two key genes, AMPD3 and TYMS, were identified and validated through ROC analysis and clinical tissue samples. A nomogram based on these genes demonstrated strong diagnostic performance. Enrichment analysis revealed their involvement in multiple pathways, including oxidative phosphorylation. Immune infiltration analysis indicated correlations with immune cells. Drug prediction identified several candidate compounds; molecular docking further confirmed strong binding affinities—AMPD3 with AM095, and TYMS with deoxyuridine monophosphate. These findings suggest that AMPD3 and TYMS are key regulators in OA-related NM and may serve as novel biomarkers and therapeutic targets.