ArticleScientific reports2021
Adenosine deaminase modulates metabolic remodeling and orchestrates joint destruction in rheumatoid arthritis.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Article
- Synovial Joint Fluid Metabolomic Profiles and Pathways Differentiate Osteoarthritis, Rheumatoid Arthritis, and Psoriatic Arthritis.Metabolites · 2026Article
- Exploring the role of adenosine deaminase in esophageal cancer and its potential for traditional Chinese medicine intervention.Frontiers in molecular biosciences · 2026Article
- Integrated Transcriptome and Metabolomics Analyses Show MYC as a Potential Therapeutic Target for Behçet's Uveitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- UnCOT-AD: Unpaired Cross-Omics Translation Enables Multi-Omics Integration for Alzheimer's Disease Prediction.Briefings in bioinformatics · 2025Article
- Immediate postoperative effects of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy using carboplatin on peritoneal tissue inflammatory and ischemic responses: an explorative porcine study.Pleura and peritoneum · 2025Article
- Medical Ozone Increases Methotrexate Effects in Rheumatoid Arthritis Through a Shared New Mechanism Which Involves Adenosine.International journal of molecular sciences · 2025Review
- The Role of Caspase-1 and Caspase-4 in Modulating Gingival Epithelial Cell Responses toPathogens (Basel, Switzerland) · 2025Article
- The association between glutathione reductase and postmenopausal osteoporosis: a retrospective study.Frontiers in endocrinology · 2025Article
- Deciphering Immunometabolic Landscape in Rheumatoid Arthritis: Integrative Multiomics, Explainable Machine Learning and Experimental Validation.Journal of inflammation research · 2025Article
- Adenosine AFrontiers in pharmacology · 2024Article
- Evidence supported by Mendelian randomization: impact on inflammatory factors in knee osteoarthritis.Frontiers in medicine · 2024Article
- In vivo phenotypic validation of adenosine receptor-dependent activity of non-adenosine drugs.Purinergic signalling · 2023Article
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- Integrated multi-omics analysis of Alzheimer's disease shows molecular signatures associated with disease progression and potential therapeutic targets.Scientific reports · 2023Article
- Vitamin B3 Biotech · 2023Article
- Prolonged administration of total glucosides of paeony improves intestinal immune imbalance and epithelial barrier damage in collagen-induced arthritis rats based on metabolomics-network pharmacology integrated analysis.Frontiers in pharmacology · 2023Article
- Integrated multi-omics analysis of Huntington disease identifies pathways that modulate protein aggregation.Disease models & mechanisms · 2022Article
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- Biomarkers of Inflammation Increase with Tau and Neurodegeneration but not with Amyloid-β in a Heterogenous Clinical Cohort.Journal of Alzheimer's disease : JAD · 2022Article
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rheumatoid Arthritis (RA) is a chronic autoimmune disease associated with inflammation and joint remodeling. Adenosine deaminase (ADA), a risk factor in RA, degrades adenosine, an anti-inflammatory molecule, resulting in an inflammatory bias. We present an integrative analysis of clinical data, cytokines, serum metabolomics in RA patients and mechanistic studies on ADA-mediated effects on in vitro cell culture models. ADA activity differentiated patients into low and high ADA sets. The levels of the cytokines TNFα, IFNγ, IL-10, TGFβ and sRANKL were elevated in RA and more pronounced in high ADA sets. Serum metabolomic analysis shows altered metabolic pathways in RA which were distinct between low and high ADA sets. Comparative analysis with previous studies shows similar pathways are modulated by DMARDs and biologics. Random forest analysis distinguished RA from control by methyl-histidine and hydroxyisocaproic acid, while hexose-phosphate and fructose-6-phosphate distinguished high ADA from low ADA. The deregulated metabolic pathways of High ADA datasets significantly overlapped with high ADA expressing PBMCs GEO transcriptomics dataset. ADA induced the death of chondrocytes, synoviocyte proliferation, both inflammation in macrophages and their differentiation into osteoclasts and impaired differentiation of mesenchymal stem cells to osteoblasts and mineralization. PBMCs expressing elevated ADA had increased expression of cytokines and P2 receptors compared to synovial macrophages which has low expression of ADA. Our data demonstrates increased cytokine levels and distinct metabolic signatures of RA based on the ADA activity, suggests an important role for ADA in the pathophysiology of RA joints and as a potential marker and therapeutic target in RA patients.
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