{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T07:11:18Z","timestamp":1715584278974},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T00:00:00Z","timestamp":1492560000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572111"],"award-info":[{"award-number":["81572111"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2017,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label \/><jats:p>Wear particle\u2010induced osteolysis is a major cause of aseptic loosening, which is one of the most common reasons for total hip arthroplasty (THA) failure. Previous studies have shown that the expression of Receptor activation of nuclear factor (NF)\u2010kB (RANKL) by fibroblasts in periprosthetic membrane played a crucial role in wear particle\u2010induced osteolysis. However, the underlying mechanism of RANKL expression remains largely unknown. In the present study, we investigated the effect of TiAl<jats:sub>6<\/jats:sub>V<jats:sub>4<\/jats:sub> particle (TiPs)\u2010induced XBP1s (spliced form of X\u2010box binding protein 1) on RANKL expression and osteoclastogenesis both in vitro and in vivo. The levels of XBP1s in peri\u2010implant membrane, animal models, and TiPs\u2010stimulated fibroblasts were determined by western blots. To assess the effect of XBP1s on RANKL expression, fibroblasts were treated with both a small interfering RNA (siRNA) and an inhibitor of XBP1 prior to exposure to TiPs. The effect of XBP1s on osteoclasts formation was determined by tartrate\u2010resistant acid phosphatase (TRAP) staining in vitro osteoclastogenesis assay and in animal models. The resorption of bone was assessed by micro\u2010computed tomography (micro\u2010CT) with three\u2010dimensional reconstruction. Our results demonstrated that XBP1s was activated in periprosthetic membrane, mouse calvaria models, and TiPs\u2010stimulated human synovial fibroblasts. Further, inhibition of XBP1s decreased the expression of RANKL and osteoclasts formation in vitro. In mouse calvaria models, both of the osteoclastogenesis and osteolysis were inhibited XBP1s inhibitor. Our results suggested that XBP1s mediated TiPs\u2010induced of RANKL expression in fibroblasts, and down regulating XBP1s may represent a potential therapy for wear particle\u2010induced osteolysis. \u00a9 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. 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