{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:03:21Z","timestamp":1792800201143,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,11,3]],"date-time":"2016-11-03T00:00:00Z","timestamp":1478131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Wear\u2010particle osteolysis affects prosthesis survival leading to implant loosening up to 70% of revisions. Therapeutic strategies are increasing, however alternative testing methods to experimentally evaluate such treatments are lacking. The aim of this study was to reproduce an <jats:italic>in vitro<\/jats:italic> osteolysis model recapitulating the events that, starting from the exposure of macrophages to polyethylene, lead to the establishment of osteoclastogenesis and inflammation. Responses to polyethylene, at 3 and 7 days, in a macrophage cell line, RAW 264.7, were determined by DNA quantification, immunofluorescence, pit assay, gene expression, cytokine production and NF\u2010kB activation. Results showed that 3 days exposure to particles could induce a significant production of Tumor Necrosis Factor alpha (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0005) and Prostaglandin E<jats:sub>2<\/jats:sub> (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.005) compared to controls. Particles also induced macrophages to spontaneously differentiate into mature and active osteoclasts, in terms of identification of multinucleated cells by Phalloidin staining and by the analysis of osteoclast\u2010specific gene markers. In particular, at 3 days polyethylene induced a significant up\u2010regulation of Nuclear Factor of Activated T\u2010cells, cytoplasmic 1, Receptor Activator of Nuclear factor Kappa\u2010B and Receptor Activator of Nuclear Factor Kappa\u2010B Ligand genes (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0005) compared to controls. At protein level, the particles induced a significant increase of Receptor Activator of Nuclear Factor Kappa\u2010B Ligand at day 7 over controls (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0005). Osteoclasts were capable to resorb bone even in absence of differentiating factors. The possible mechanism, beside spontaneous osteoclastogenesis mediated by wear debris, was identified in an autocrine up\u2010regulation of Receptor activator of nuclear factor kappa\u2010B ligand gene expression and protein synthesis. \u00a9 2016 Wiley Periodicals, Inc. 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