{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:12:14Z","timestamp":1790741534266,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,8,29]],"date-time":"2012-08-29T00:00:00Z","timestamp":1346198400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Activation of myeloid cells by orthopedic particulate debris is a key event in the pathogenesis of periprosthetic osteolysis and implant loosening after total joint replacement (TJR). Several lines of evidence implicate NACHT, LRR, and PYD domains\u2010containing protein 3 (NALP3) inflammasome\u2010mediated production of interleukin 1 beta (IL\u20101\u03b2) in the pathogenesis of clinical disorders ascribable to foreign particulate materials, including asbestos, silica, and urate crystals. Recent reports indicate that orthopedic polymer products and metallic particulates and ions may activate the same pathway. Here, we investigated the contribution of the NALP3 inflammasome to the pathogenesis of peri\u2010implant osteolysis. Pharmaceutical and genetic perturbations of caspase\u20101 and inflammasome components were used to assess the role of the NALP3 inflammasome in IL\u20101\u03b2 production and osteoclast formation by human monocytes and mouse macrophages in response to polymethylmethacrylate (PMMA) particle phagocytosis. The role of caspase\u20101 in a mouse calvarial model of particle\u2010mediated osteolysis was assessed using \u00b5CT. Phagocytosis of PMMA particles induces caspase\u20101 dependent release of IL\u20101\u03b2 from human monocytes and mouse macrophages. Importantly, using macrophages from mice deficient in components of the NALP3 inflammasome, we show PMMA\u2010induced IL\u20101\u03b2 production is strictly dependent on these components. Mice lacking caspase\u20101, the sole effector of the NALP3 inflammasome, show reduced orthopedic wear particle\u2010induced calvarial osteolysis compared to wild\u2010type controls. Absence of NALP3 inflammasome components fails to alter osteoclast formation in vitro. Our findings identify the NALP3 inflammasome as a critical mediator of orthopedic wear\u2010induced osteolysis and as a viable therapeutic target for the treatment of periprosthetic osteolysis. \u00a9 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:73\u201380, 2012<\/jats:p>","DOI":"10.1002\/jor.22190","type":"journal-article","created":{"date-parts":[[2012,8,29]],"date-time":"2012-08-29T14:56:23Z","timestamp":1346252183000},"page":"73-80","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation"],"prefix":"10.1002","volume":"31","author":[{"given":"Lyndsey","family":"Burton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Paget","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus B.","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Bohnert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan J.","family":"Nestor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P.","family":"Sculco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Santambrogio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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