ArticleArthritis research & therapy2018
Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rheumatoid arthritis fibroblast-like synoviocytes.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Association between the Platelet-Derived Growth Factor/Platelet-Derived Growth Factor Receptor System and Risk of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.Computational and mathematical methods in medicine · 2022Pooled it
- Epigenetic Modulation of IL-7 and IL-10: Toward Personalized Immune Therapies in Viral Epidemics.Journal of immunology research · 2026Article
- Methotrexate promotes the release of granulocyte-macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 signaling.Arthritis research & therapy · 2024Article
- An Overview of Methotrexate Indications in Skin Diseases.Medicina (Kaunas, Lithuania) · 2024Review
- Methotrexate inhibits BMP4 and abrogates the hypertrophic chondrocyte phenotype of synovial fibroblasts in juvenile idiopathic arthritis.Pediatric rheumatology online journal · 2024Article
- Demethylation of CDKN2A in systemic lupus erythematosus and rheumatoid arthritis: a blood biomarker for diagnosis and assessment of disease activity.Clinical rheumatology · 2023Article
- Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis.Clinical immunology (Orlando, Fla.) · 2023Article
- A large-scale Boolean model of the rheumatoid arthritis fibroblast-like synoviocytes predicts drug synergies in the arthritic joint.NPJ systems biology and applications · 2023Article
- Effect of manipulation on cartilage in rats with knee osteoarthritis based on the Rho-associated protein kinase/LIM kinase 1/Cofilin signaling pathways.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2022Article
- Platelet signaling at the nexus of innate immunity and rheumatoid arthritis.Frontiers in immunology · 2022Review
- Detecting potential mechanism of vitamin D in treating rheumatoid arthritis based on network pharmacology and molecular docking.Frontiers in pharmacology · 2022Article
- Methotrexate and theaflavin-3, 3'-digallate synergistically restore the balance between apoptosis and autophagy in synovial fibroblast of RA: an ex vivo approach with cultured human RA FLS.Inflammopharmacology · 2021Article
- Signalling and putative therapeutic molecules on the regulation of synoviocyte signalling in rheumatoid arthritis.Bone & joint research · 2021Article
- EZH2 Inhibition Interferes With the Activation of Type I Interferon Signaling Pathway and Ameliorates Lupus Nephritis in NZB/NZW F1 Mice.Frontiers in immunology · 2021Article
- Article
- Methotrexate an Old Drug with New Tricks.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundA key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro.
methodsPrimary FLS from patients with RA or osteoarthritis were stimulated with the mitogen platelet-derived growth factor (PDGF) and the cytokine interleukin-1β (IL-1β) in the presence or absence of MTX. Cells were then subjected to qPCR for gene expression and cell cycle analysis by flow cytometry.
resultsStimulation with PDGF and IL-1β increased the percentage of FLS in the G2/M phase and shifted the cell morphology to a dendritic shape. These effects were inhibited by MTX. Furthermore, PDGF + IL-1β reduced LBH mRNA expression. However, MTX treatment yielded significantly higher transcript levels of LBH, and of CDKN1A (p21) and TP53 (p53), compared to untreated samples upon mitogen stimulation. The expression of DNA methyltransferase-1 (DNMT1) was also higher in the presence of MTX and there was strong correlation between DNMT1 and LBH expression.
conclusionsTherapeutic concentrations of MTX abolish the effects of PDGF and IL-1β on tumor suppressor expression and inhibit mitogen-promoted FLS proliferation. These data demonstrate novel and important effects of MTX on pathogenic effector cells in the joint, which might involve epigenetic mechanisms.
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