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.

• Publication year

  2025

• Venue

  Nucleosides, Nucleotides & Nucleic Acids

• Publication date

  2025-11-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1080/15257770.2025.2577918PMID 41217154
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The pentose phosphate pathway controls oxidative protein folding and prevents ferroptosis in chondrocytes

  2025cited by this paper
• Beyond wear and tear at the joint.

  2025cited by this paper
• Targeting nucleotide metabolic pathways in colorectal cancer by integrating scRNA-seq, spatial transcriptome, and bulk RNA-seq data

  2024cited by this paper
• Association of Synovial Innate Immune Exhaustion With Worse Pain in Knee Osteoarthritis

  2024cited by this paper
• Exercise for osteoarthritis of the knee.

  2024cited by this paper
• Cross-talk of inflammation and cellular senescence: a new insight into the occurrence and progression of osteoarthritis

  2024cited by this paper
• Harnessing nucleotide metabolism and immunity in cancer: a tumour microenvironment perspective

  2024cited by this paper
• Krill Oil for Knee Osteoarthritis: A Randomized Clinical Trial.

  2024cited by this paper
• Downregulation of extramitochondrial BCKDH and its uncoupling from AMP deaminase in type 2 diabetic OLETF rat hearts

  2023cited by this paper
• NAD+ regulates nucleotide metabolism and genomic DNA replication

  2023cited by this paper
• A nomogram for predicting prognosis of patients with cervical cerclage

  2023cited by this paper
• Erythrocyte ENT1-AMPD3 Axis is an Essential Purinergic Hypoxia Sensor and Energy Regulator Combating CKD in a Mouse Model

  2023cited by this paper
• Nucleotide metabolism: a pan-cancer metabolic dependency

  2023cited by this paper
• Osteoarthritis: pathogenic signaling pathways and therapeutic targets

  2023cited by this paper
• Current understanding of osteoarthritis pathogenesis and relevant new approaches

  2022cited by this paper
• A plant-derived natural photosynthetic system for improving cell anabolism

  2022cited by this paper
• Dysregulated energy metabolism impairs chondrocyte function in osteoarthritis.

  2022cited by this paper
• Dummy regression to predict dry fiber in Agave lechuguilla Torr. in two large-scale bioclimatic regions in Mexico

  2022cited by this paper
• Identification of Hub Genes Associated With Non-alcoholic Steatohepatitis Using Integrated Bioinformatics Analysis

  2022cited by this paper
• Targeting nucleotide metabolism: a promising approach to enhance cancer immunotherapy

  2022cited by this paper
• ggtranscript: an R package for the visualization and interpretation of transcript isoforms using ggplot2

  2022cited by this paper
• MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure

  2022cited by this paper
• Metabolic regulation of skeletal cell fate and function in physiology and disease

  2021cited by this paper
• Worldwide Traceability of Antibiotic Residues from Livestock in Wastewater and Soil: A Systematic Review

  2021cited by this paper
• Histone N-terminal acetyltransferase NAA40 links one-carbon metabolism to chemoresistance

  2021cited by this paper
• Network Pharmacology-Based Systematic Analysis of Molecular Mechanisms of Geranium wilfordii Maxim for HSV-2 Infection

  2021cited by this paper
• clusterProfiler 4.0: A universal enrichment tool for interpreting omics data

  2021cited by this paper
• Early-stage symptomatic osteoarthritis of the knee — time for action

  2021cited by this paper
• Nicotinamide adenine dinucleotide metabolism in the immune response, autoimmunity and inflammageing

  2021cited by this paper
• Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review.

  2021cited by this paper
• AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings

  2021cited by this paper
• The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis.

  2020cited by this paper
• MUC1 Oncoprotein Mitigates ER Stress via CDA-mediated Reprogramming of Pyrimidine Metabolism

  2020cited by this paper
• Cellular Senescence: Defining a Path Forward.

  2019cited by this paper
• HIF-1α metabolically controls collagen synthesis and modification in chondrocytes

  2019cited by this paper
• Clinical implications of macrophage dysfunction in the development of osteoarthritis of the knee.

  2019cited by this paper
• Statistical predictions with glmnet

  2019cited by this paper
• Pathway analysis of genetic variants in folate‐mediated one‐carbon metabolism‐related genes and survival in a prospectively followed cohort of colorectal cancer patients

  2018cited by this paper
• TLR8 activation and inhibition by guanosine analogs in RNA: Importance of functional groups and chain length.

  2018cited by this paper
• GOT1-mediated anaplerotic glutamine metabolism regulates chronic acidosis stress in pancreatic cancer cells.

  2017cited by this paper
• Metabolic regulation of inflammation

  2017cited by this paper
• CXCR3/CXCL10 Axis Regulates Neutrophil–NK Cell Cross-Talk Determining the Severity of Experimental Osteoarthritis

  2017cited by this paper
• xCell: digitally portraying the tissue cellular heterogeneity landscape

  2017cited by this paper
• Structural Analysis Reveals that Toll-like Receptor 7 Is a Dual Receptor for Guanosine and Single-Stranded RNA.

  2016cited by this paper
• Assessing the Clinical Impact of Risk Prediction Models With Decision Curves: Guidance for Correct Interpretation and Appropriate Use.

  2016cited by this paper
• Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis

  2016cited by this paper
• A guide to immunometabolism for immunologists

  2016cited by this paper
• Ageing and the pathogenesis of osteoarthritis

  2016cited by this paper
• MTHFD1 regulates nuclear de novo thymidylate biosynthesis and genome stability.

  2016cited by this paper
• Oxidative Stress and Response to Thymidylate Synthase-Targeted Antimetabolites

  2015cited by this paper
• Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use.

  2015cited by this paper
• limma powers differential expression analyses for RNA-sequencing and microarray studies

  2015cited by this paper
• Associations between single-nucleotide polymorphisms of RFC-1, GGH, MTHFR , TYMS, and TCII genes and the efficacy and toxicity of methotrexate treatment in patients with rheumatoid arthritis.

  2015cited by this paper
• CD73 and AMPD3 deficiency enhance metabolic performance via erythrocyte ATP that decreases hemoglobin oxygen affinity

  2015cited by this paper
• Emerging regulators of the inflammatory process in osteoarthritis

  2015cited by this paper
• Regulation of mammalian nucleotide metabolism and biosynthesis

  2015cited by this paper
• Advanced Heat Map and Clustering Analysis Using Heatmap3

  2014cited by this paper
• Genome-wide analysis of methotrexate pharmacogenomics in rheumatoid arthritis shows multiple novel risk variants and leads for TYMS regulation

  2014cited by this paper
• Direct in vivo evidence of activated macrophages in human osteoarthritis.

  2013cited by this paper
• Coming of age: molecular drivers of aging and therapeutic opportunities.

  2013cited by this paper
• Decreased levels of nucleotide pyrophosphatase phosphodiesterase 1 are associated with cartilage calcification in osteoarthritis and trigger osteoarthritic changes in mice

  2012cited by this paper
• pROC: an open-source package for R and S+ to analyze and compare ROC curves

  2011cited by this paper
• Ligand docking and binding site analysis with PyMOL and Autodock/Vina

  2010cited by this paper
• Exercise for Osteoarthritis of the Knee

  2010cited by this paper
• Linking functional decline of telomeres, mitochondria and stem cells during ageing

  2010cited by this paper
• 4-Hydroxynonenal induces apoptosis in human osteoarthritic chondrocytes: the protective role of glutathione-S-transferase

  2008cited by this paper
• Osteoarthritis

  2006cited by this paper
• Calcium activates erythrocyte AMP deaminase [isoform E (AMPD3)] through a protein-protein interaction between calmodulin and the N-terminal domain of the AMPD3 polypeptide.

  2005cited by this paper
• Cytoscape: a software environment for integrated models of biomolecular interaction networks.

  2003cited by this paper
• Molecular analysis of mouse Ampd3 gene encoding heart-type isoform of AMP deaminase.

  1997cited by this paper

• No citing papers are available for this paper.