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However, the molecular mechanism underlying this phenomenon is poorly understood. In this study, we analyzed the involvement of the GSK-3<jats:italic>\u03b2\/\u03b2<\/jats:italic>-catenin signal pathway, which is important for bone formation in this pathological condition. We established a titanium (Ti) particle-stressed murine MC3T3-E1 cell culture system and calvariae osteolysis model to test the hypothesis that Ti particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3<jats:italic>\u03b2\/\u03b2<\/jats:italic>-catenin signal pathway. Our findings showed that Ti particles reduced osteogenic differentiation induced by osteogenesis-related gene expression, alkaline phosphatase activity and matrix mineralization, as well as pSer9-GSK-3<jats:italic>\u03b2<\/jats:italic> expression and <jats:italic>\u03b2<\/jats:italic>-catenin signal activity. Downregulation of GSK-3<jats:italic>\u03b2<\/jats:italic> activity attenuated Ti particle-induced osteogenic inhibition, whereas the <jats:italic>\u03b2<\/jats:italic>-catenin inhibitor reversed this protective effect. Moreover, the GSK-3<jats:italic>\u03b2\/\u03b2<\/jats:italic>-catenin signal pathway mediated the upregulation of RANKL and downregulation of OPG in Ti particle-stressed MC3T3-E1 cells. In addition, our <jats:italic>in vivo<\/jats:italic> results showed that Ti particles induced bone loss via regulating GSK-3<jats:italic>\u03b2<\/jats:italic> and <jats:italic>\u03b2<\/jats:italic>-catenin signals. Based on these results, we concluded that the GSK-3<jats:italic>\u03b2\/\u03b2<\/jats:italic>-catenin signal pathway mediates the adverse effects of Ti particles on osteoblast differentiation and bone destruction, and can be used as a potential therapeutic target for the treatment of peri-prosthetic osteolysis.<\/jats:p>","DOI":"10.1038\/cddis.2017.275","type":"journal-article","created":{"date-parts":[[2017,6,15]],"date-time":"2017-06-15T12:43:39Z","timestamp":1497530619000},"page":"e2878-e2878","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Titanium particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3\u03b2\/\u03b2-catenin signal pathway"],"prefix":"10.1038","volume":"8","author":[{"given":"Ye","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyang","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiexing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaozeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechun","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,15]]},"reference":[{"key":"BFcddis2017275_CR1","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.2106\/JBJS.H.00168","volume":"91","author":"CJ Della Valle","year":"2009","unstructured":"Della Valle CJ, Mesko NW, Quigley L, Rosenberg AG, Jacobs JJ, Galante JO . 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