ArticlePLoS computational biology2022
Metabolic reprogramming in Rheumatoid Arthritis Synovial Fibroblasts: A hybrid modeling approach.
Article in PLoS computational biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Identification of Diagnostic Biomarkers Among Metabolism-related Genes in Rheumatoid Arthritis: Insights into Immune Landscape and Molecular Subtype Characterization.Applied biochemistry and biotechnology · 2026Article
- Lactate programs CRIP1 protein lactylation to drive synovial proliferation in rheumatoid arthritis.JCI insight · 2026Article
- Digital twins to accelerate target identification and drug development for immune-mediated disorders.FEBS open bio · 2026Review
- MMP3C v2: a network-based framework decoding metabolic plasticity in rheumatoid arthritis, enabling accurate diagnosis and uncovering cell-type-specific metabolic rewiring.Briefings in bioinformatics · 2026Article
- LIN28A‒let-7b axis drives the aggressive and proinflammatory phenotype of rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2026Article
- The SjD Map: an interactive pathway tour into Sjögren's disease signalling mechanisms.NPJ systems biology and applications · 2026Article
- The gut-joint axis in gout: microbial outer membrane vesicles and mFrontiers in immunology · 2026Review
- Roles of immune cell metabolism in rheumatoid arthritis.Frontiers in immunology · 2026Review
- Rewiring immunity in rheumatoid arthritis: metabolic and epigenetic therapeutic strategies.Frontiers in pharmacology · 2026Review
- Identification and Immune Landscape Analysis of Fatty Acid Metabolism-related Genes Associated with Rheumatoid Arthritis.International journal of medical sciences · 2026Article
- Mechanism of HIF-1α-mediated angiogenesis in rheumatoid arthritis and progress of natural medicine interventions.Frontiers in pharmacology · 2026Review
- Unveiling the Therapeutic Potential: Targeting Fibroblast-like Synoviocytes in Rheumatoid Arthritis.Expert reviews in molecular medicine · 2025Review
- Integrated analysis of the relationship between metabolic pathways and immune infiltration in rheumatoid arthritis.Frontiers in immunology · 2025Article
- BACH1 as a key driver in rheumatoid arthritis fibroblast-like synoviocytes identified through gene network analysis.Life science alliance · 2025Article
- Overlapping genes connect rheumatoid arthritis and head and neck cancer: coincidence or shared immune pathophysiology?Frontiers in medicine · 2025Article
- Immune digital twins for complex human pathologies: applications, limitations, and challenges.NPJ systems biology and applications · 2024Review
- MetaLo: metabolic analysis of Logical models extracted from molecular interaction maps.Journal of integrative bioinformatics · 2024Article
- Overview of mechanisms and novel therapies on rheumatoid arthritis from a cellular perspective.Frontiers in immunology · 2024Review
- Reversing pathological cell states: the road less travelled can extend the therapeutic horizon.Trends in cell biology · 2023Review
- The therapeutic effects of gingival mesenchymal stem cells and their exosomes in a chimeric model of rheumatoid arthritis.Arthritis research & therapy · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rheumatoid Arthritis (RA) is an autoimmune disease characterized by a highly invasive pannus formation consisting mainly of Synovial Fibroblasts (RASFs). This pannus leads to cartilage, bone, and soft tissue destruction in the affected joint. RASFs' activation is associated with metabolic alterations resulting from dysregulation of extracellular signals' transduction and gene regulation. Deciphering the intricate mechanisms at the origin of this metabolic reprogramming may provide significant insight into RASFs' involvement in RA's pathogenesis and offer new therapeutic strategies. Qualitative and quantitative dynamic modeling can address some of these features, but hybrid models represent a real asset in their ability to span multiple layers of biological machinery. This work presents the first hybrid RASF model: the combination of a cell-specific qualitative regulatory network with a global metabolic network. The automated framework for hybrid modeling exploits the regulatory network's trap-spaces as additional constraints on the metabolic network. Subsequent flux balance analysis allows assessment of RASFs' regulatory outcomes' impact on their metabolic flux distribution. The hybrid RASF model reproduces the experimentally observed metabolic reprogramming induced by signaling and gene regulation in RASFs. Simulations also enable further hypotheses on the potential reverse Warburg effect in RA. RASFs may undergo metabolic reprogramming to turn into "metabolic factories", producing high levels of energy-rich fuels and nutrients for neighboring demanding cells through the crucial role of HIF1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.