ArticleArthritis & rheumatology (Hoboken, N.J.)2015
Brief Report: Methotrexate Prevents Wear Particle-Induced Inflammatory Osteolysis in Mice Via Activation of Adenosine A2A Receptor.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- The Role and Mechanistic Effects of Methotrexate in the Treatment of Rheumatoid Arthritis.European journal of rheumatology · 2025Article
- Article
- The different effects of four adenosine receptors in liver fibrosis.Frontiers in pharmacology · 2024Article
- Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB-inhibitor on chronic inflammatory osteolysis in aged mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- International Union of Basic and Clinical Pharmacology. CXII: Adenosine Receptors: A Further Update.Pharmacological reviews · 2022Review
- Short-wave enhances mesenchymal stem cell recruitment in fracture healing by increasing HIF-1 in callus.Stem cell research & therapy · 2020Article
- Signaling of the Purinergic System in the Joint.Frontiers in pharmacology · 2019Review
- Bone regeneration in critical bone defects using three-dimensionally printed β-tricalcium phosphate/hydroxyapatite scaffolds is enhanced by coating scaffolds with either dipyridamole or BMP-2.Journal of biomedical materials research. Part B, Applied biomaterials · 2017Article
- Regulation of bone and cartilage by adenosine signaling.Purinergic signalling · 2016Review
- Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium influx into osteoclast progenitors.Journal of bone and mineral metabolism · 2016Article
- Netrin-1 is highly expressed and required in inflammatory infiltrates in wear particle-induced osteolysis.Annals of the rheumatic diseases · 2016Article
- Purinergic regulation of the immune system.Nature reviews. Immunology · 2016Review
- A review of UHMWPE wear-induced osteolysis: the role for early detection of the immune response.Bone research · 2016Review
- Direct or indirect stimulation of adenosine A2A receptors enhances bone regeneration as well as bone morphogenetic protein-2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- ER Stress Mediates TiAl6V4 Particle-Induced Peri-Implant Osteolysis by Promoting RANKL Expression in Fibroblasts.PloS one · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
objectiveAdenosine, acting at the A2A receptor, mediates the antiinflammatory effects of methotrexate (MTX) in models of inflammation. We previously reported that A2A receptor ligation diminishes wear particle-driven osteolysis. The aim of this study was to investigate whether MTX treatment could prevent bone resorption caused by inflammatory osteolysis.
methodsC57BL/6 mice (6-8 weeks old) received intraperitoneal injections of 1 mg/kg MTX (n = 20) or 0.9% saline (n = 10), starting 2 weeks prior to surgical implantation of 3 mg of wear particles (ultrahigh molecular weight polyethylene [UHMWPE] particles). The MTX-treated mice received daily injections of vehicle or ZM241385 at the surgical site until they were killed, 14 days later. XenoLight RediJect Bone Probe 680 was injected intravenously, and fluorescence analysis of the calvaria using an IVIS imaging system was performed to assess bone formation. Micro-computed tomography (micro-CT) and immunostaining for osteoclast and osteoblast markers were performed.
resultsImplantation of wear particles induced bone pitting and thinning, as shown by micro-CT. MTX treatment markedly reduced osteolysis, and this effect was abrogated by treatment with the A2A receptor antagonist ZM241385. Implantation of UHMWPE reduced new bone formation, and MTX treatment restored new bone formation, an effect that was completely reversed by treatment with ZM241385. Histologic examination of particle-exposed calvariae demonstrated that MTX prevented accumulation of an inflammatory infiltrate at the site of particle implantation, increased the number of osteoblasts, and reduced the number of osteoclasts at the site of inflammation, an effect that was reversed by treatment with ZM241385.
conclusionMTX reduces inflammatory osteolysis indirectly via stimulation of A2A receptor and may represent a novel approach to enhance orthopedic implant survival, delaying or eliminating the need for revision arthroplasty surgery.
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