Trial reportArthritis research & therapy2013
Synovial membrane immunohistology in early-untreated rheumatoid arthritis reveals high expression of catabolic bone markers that is modulated by methotrexate.
Trial report in Arthritis research & therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Efficacy of methotrexate in reducing the risk of bone erosion in patients with rheumatoid arthritis: a systematic review of randomized controlled trials.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- Low-Dose Methotrexate and Bone Health: Pathophysiological and Clinical Perspectives.Journal of clinical medicine · 2026Review
- Mechanisms of osteoclast activation in inflammatory bone loss in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Methotrexate inhibits BMP4 and abrogates the hypertrophic chondrocyte phenotype of synovial fibroblasts in juvenile idiopathic arthritis.Pediatric rheumatology online journal · 2024Article
- Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis.Clinical rheumatology · 2024Article
- Toward Overcoming Treatment Failure in Rheumatoid Arthritis.Frontiers in immunology · 2021Review
- Methotrexate inhibits effects of platelet-derived growth factor and interleukin-1β on rheumatoid arthritis fibroblast-like synoviocytes.Arthritis research & therapy · 2018Article
- The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.Clinical reviews in allergy & immunology · 2016Review
- Effect of Osteoprotegerin and Dickkopf-Related Protein 1 on Radiological Progression in Tightly Controlled Rheumatoid Arthritis.PloS one · 2016Observational
- Assessment of the Effect of Methotrexate Therapy on Bone Metabolism in Patients with Rheumatoid Arthritis.Archivum immunologiae et therapiae experimentalis · 2015Article
- Serum RANKL levels associate with anti- citrullinated protein antibodies in early untreated rheumatoid arthritis and are modulated following methotrexate.Arthritis research & therapy · 2015Article
- Inhibitory Effect of a Novel Antirheumatic Drug T-614 on the IL-6-Induced RANKL/OPG, IL-17, and MMP-3 Expression in Synovial Fibroblasts from Rheumatoid Arthritis Patients.BioMed research international · 2015Article
- Impact of dietary aromatic amino acids on osteoclastic activity.Calcified tissue international · 2014Article
- Synergistic Effects of BTK Inhibitor HM71224 and Methotrexate in a Collagen-induced Arthritis Rat Model.In vivo (Athens, Greece)Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionWe aimed to investigate the expression and therapeutic modulation of the receptor activator of the NF-κB ligand (RANKL) system in early-untreated rheumatoid arthritis (RA).
methodsIn this study, 15 patients with newly diagnosed RA (median symptom duration 7 months) were started on methotrexate (MTX) 20 mg weekly. Synovial biopsies were obtained by needle arthroscopy at baseline and 8 weeks after initiation of therapy. X-rays of the hands and feet were obtained at baseline and 1 year after diagnosis. Immunohistochemistry was performed to detect RANKL, receptor activator of nuclear factor-κB (RANK) and osteoprotegerin (OPG) in the synovial biopsies. The in vitro effect of MTX was tested on RA-derived primary fibroblasts and the osteoblasts-like osteosarcoma cell line (rtPCR, Western blot and ELISA) and in osteoclasts (tartrate-resistant acid phosphatase staining and dentine pit formation assay).
resultsMTX decreased synovial cellularity as well as RANK expression and the RANKL/OPG ratio. We confirmed this effect by a decrease of the mRNA and protein RANKL/OPG ratio in synovial-derived fibroblasts and osteoblasts-like tumoral cells exposed in vitro to methotrexate. Supernatants from MTX treated osteoblasts-like tumoral cells prevented pre-osteoclast formation in the absence of exogenous RANKL. Furthermore, MTX blocked osteoclastogenesis from peripheral blood mononuclear cells despite the presence of macrophage colony stimulating factor and RANKL, which indicates that MTX directly inhibits osteoclastogenesis.
conclusionsThe synovial membrane of early-untreated RA is characterized by a high RANKL/OPG ratio that can be reversed by methotrexate.
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