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As sentinels of the innate immune system, macrophages are central to the recognition and initiation of the inflammatory cascade, which results in the activation of bone resorbing osteoclasts. Toll\u2010like receptors (TLRs) are involved in the recognition of pathogen\u2010associated molecular patterns and danger\u2010associated molecular patterns. Experimentally, polymethylmethacrylate and polyethylene (PE) particles have been shown to activate macrophages via the TLR pathway. The specific TLRs involved in PE particle\u2010induced osteolysis remain largely unknown. We hypothesized that TLR\u20102, \u20104, and \u20109 mediated responses play a critical role in the development of PE wear particle\u2010induced osteolysis in the murine calvarium model. To test this hypothesis, we first demonstrated that PE particles caused observable osteolysis, visible by microCT and bone histomorphometry when the particles were applied to the calvarium of C57BL\/6 mice. The number of TRAP positive osteoclasts was significantly greater in the PE\u2010treated group when compared to the control group without particles. Finally, using immunohistochemistry, TLR\u20102 and TLR\u20104 were highly expressed in PE particle\u2010induced osteolytic lesions, whereas TLR\u20109 was downregulated. TLR\u20102 and \u20104 may represent novel therapeutic targets for prevention of wear particle\u2010induced osteolysis and accompanying TJR failure. \u00a9 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3004\u20133011, 2014.<\/jats:p>","DOI":"10.1002\/jbm.a.34972","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:14:57Z","timestamp":1381540497000},"page":"3004-3011","source":"Crossref","is-referenced-by-count":32,"title":["Toll\u2010like receptors\u20102 and 4 are overexpressed in an experimental model of particle\u2010induced osteolysis"],"prefix":"10.1002","volume":"102","author":[{"given":"Roberto D.","family":"Valladares","sequence":"first","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery Stanford University School of Medicine Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Nich","sequence":"additional","affiliation":[{"name":"Orthopaedic Research Laboratories, Department of Orthopaedic Surgery Stanford University School of Medicine Stanford California"},{"name":"Laboratoire de Biom\u00e9canique et 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