ArticleRMD open2024
Methotrexate inhibits glucocorticoids-induced osteoclastogenesis via activating IFN-γR/STAT1 pathway in the treatment of rheumatoid arthritis.
Article in RMD open, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Betulinic acid alleviates ankylosing spondylitis and remodels Th17/Treg-associated immune landscapes revealed by single-cell transcriptomics.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Betulinic acid alleviates ankylosing spondylitis and remodels Th17/Treg-associated immune landscapes revealed by single-cell transcriptomics.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Osteoporosis in rheumatoid arthritis: a new perspective on risk factors and clinical prediction models.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Review
- Therapeutic effects of ginkgetin on rheumatoid arthritis: evidence from network pharmacology and experimental validation.Clinical rheumatology · 2026Article
- Emodin Attenuates Rheumatoid Arthritis by Modulating the NF-κB/HIF-1α/VEGF Signaling Pathway.International journal of molecular sciences · 2026Article
- OptiSyn: an interpretable, multi-omics-driven graph convolutional network framework for synergy-oriented drug combination design in disease treatment.Chinese medicine · 2026Article
- Nitazoxanide alleviates collagen-induced arthritis by inhibiting STAT3-dependent Th17 cell differentiation and inflammatory cytokines production.Frontiers in pharmacology · 2026Article
- Lipid metabolism at the intersection of rheumatoid arthritis and atherosclerosis.Frontiers in immunology · 2026Review
- The Role and Mechanistic Effects of Methotrexate in the Treatment of Rheumatoid Arthritis.European journal of rheumatology · 2025Article
- Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveal macrophage subpopulation characteristics and the role of STAT1 in rheumatoid arthritis.Journal of translational medicine · 2025Article
- Association between age at first birth and risk of rheumatoid arthritis in women: Evidence from NHANES 2011-2020.PloS one · 2025Article
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Authors and funding
8 authors.
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Abstract
objectivesRheumatoid arthritis (RA) is a chronic autoimmune disease characterised by the synovitis and bone erosion. The combination therapy of glucocorticoids (GCs) and methotrexate (MTX) is recommended in early RA management, although the precise underlying mechanism of action remains unclear. This study is aimed to clarify the mechanism of MTX in combined with GC in treating RA.
methodsGC-induced osteoporosis (GIOP) mouse model was used to investigate the bone-protective role of MTX. Lipopolysaccharide-induced arthritis mouse model was used to evaluate the anti-inflammatory effects of GCs and MTX. Functional role of MTX on osteoclastogenesis was assessed by trap staining and micro-computer tomography. Western blot, RT-qPCR and coimmunoprecipitation were used to explore the underlying mechanisms.
resultsWe demonstrate that GCs, but not MTX, rapidly inhibited synovitis in arthritis model. MTX treatment was observed to inhibit osteoclastogenesis induced by GC in vitro and mitigate bone loss attributed by GIOP. GCs were found to augment the interaction between the membrane GC receptor (mGR) and signal transducer and activator of transcription 1 (STAT1), leading to the suppression of IFN-γR/STAT1 signalling pathways. Interestingly, MTX was found to inhibit osteoclastogenesis induced by GCs through the enhancement of the A2AR and IFN-γR interaction, thereby activating the IFN-γR/STAT1 signalling cascade. Consequently, this process results in a reduction in the mGR and STAT1 interaction.
conclusionsOur study provides compelling evidence that MTX can make GCs effectively to suppress synovitis and reduce bone loss induced by GCs. This sheds light on the potential mechanistic insights underlying the efficacy of GCs in conjunction with MTX for treating RA.
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