{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T19:17:53Z","timestamp":1771355873820,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,2,25]],"date-time":"2015-02-25T00:00:00Z","timestamp":1424822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["AR-56672"],"award-info":[{"award-number":["AR-56672"]}]},{"name":"NIH","award":["AR-54897"],"award-info":[{"award-number":["AR-54897"]}]},{"name":"NIH","award":["AR-046121"],"award-info":[{"award-number":["AR-046121"]}]},{"name":"NIH","award":["RC1-HL-100815"],"award-info":[{"award-number":["RC1-HL-100815"]}]},{"name":"New York University-Health and Hospitals Corporation (NYU-HHC) Clinical and Translational Science Institute"},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences, NIH","doi-asserted-by":"crossref","award":["UL1-TR-000038"],"award-info":[{"award-number":["UL1-TR-000038"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"name":"New York University Cancer Institute Center"},{"DOI":"10.13039\/100000054","name":"National Cancer Institute, NIH","doi-asserted-by":"crossref","award":["5-P30CA16087-310"],"award-info":[{"award-number":["5-P30CA16087-310"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Takeda"},{"DOI":"10.13039\/100006436","name":"Celgene","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006436","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Gilead Pharmaceuticals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Adenosine, acting at the A<jats:sub>2A<\/jats:sub> receptor, mediates the antiinflammatory effects of methotrexate (MTX) in models of inflammation. We previously reported that A<jats:sub>2A<\/jats:sub> receptor ligation diminishes wear particle\u2013driven osteolysis. The aim of this study was to investigate whether MTX treatment could prevent bone resorption caused by inflammatory osteolysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6 mice (6\u20138 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\u2010treated 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\u2013computed tomography (micro\u2010CT) and immunostaining for osteoclast and osteoblast markers were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Implantation of wear particles induced bone pitting and thinning, as shown by micro\u2010CT. MTX treatment markedly reduced osteolysis, and this effect was abrogated by treatment with the A<jats:sub>2A<\/jats:sub> 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\u2010exposed 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MTX reduces inflammatory osteolysis indirectly via stimulation of A<jats:sub>2A<\/jats:sub> receptor and may represent a novel approach to enhance orthopedic implant survival, delaying or eliminating the need for revision arthroplasty surgery.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.38971","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T10:27:41Z","timestamp":1419244061000},"page":"849-855","source":"Crossref","is-referenced-by-count":24,"title":["Brief Report: Methotrexate Prevents Wear Particle\u2013Induced Inflammatory Osteolysis in Mice Via Activation of Adenosine A<sub>2A<\/sub> Receptor"],"prefix":"10.1002","volume":"67","author":[{"given":"Ar\u00e1nzazu","family":"Mediero","sequence":"first","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Perez\u2010Aso","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuere","family":"Wilder","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce N.","family":"Cronstein","sequence":"additional","affiliation":[{"name":"New York University School of Medicine New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,2,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001591"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003393"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198503283121303"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.5"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22643"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00085"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10766"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-231233"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp400357v"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.10.017"},{"key":"e_1_2_8_13_1","first-page":"S948","article-title":"Inhibition of osteoclast formation by adenosine A2A receptor is due to inhibition of NF\u03baB nuclear translocation by a PKA\u2010mediated mechanism [abstract]","volume":"63","author":"Mediero A","year":"2011","journal-title":"Arthritis Rheum"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-13-251"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.M.00545"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3109\/17453671003685418"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38971","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.38971","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.38971","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:41:39Z","timestamp":1759930899000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.38971"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,25]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1002\/art.38971"],"URL":"https:\/\/doi.org\/10.1002\/art.38971","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,25]]}}}