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The host response to wear debris promotes bone resorption and impairs bone formation. We previously demonstrated that icariin suppressed wear-debris-induced osteoclastogenesis and attenuated particle-induced osteolysis <jats:italic>in vivo<\/jats:italic>. Whether icariin promotes bone formation in a wear-debris-induced osteolytic site remains unclear. Here, we demonstrated that icariin significantly attenuated titanium-particle inhibition of osteogenic differentiation of mesenchymal stem cells (MSCs). Additionally, icariin increased bone mass and decreased bone loss in titanium-particle-induced osteolytic sites. Mechanistically, icariin inhibited decreased \u03b2-catenin stability induced by titanium particles <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. To confirm icariin mediated its bone-protective effects via the Wnt\/\u03b2-catenin signaling pathway, we demonstrated that ICG-001, a selective Wnt\/\u03b2-catenin inhibitor, attenuated the effects of icariin on MSC mineralization <jats:italic>in vitro<\/jats:italic> and bone formation <jats:italic>in vivo<\/jats:italic>. Therefore, icariin could induce osteogenic differentiation of MSCs and promote new bone formation at a titanium-particle-induced osteolytic site via activation of the Wnt\/\u03b2-catenin signaling pathway. These results further support the protective effects of icariin on particle-induced bone loss and provide novel mechanistic insights into the recognized bone-anabolic effects of icariin and an evidence-based rationale for its use in PIO treatment.<\/jats:p>","DOI":"10.1038\/srep23827","type":"journal-article","created":{"date-parts":[[2016,3,31]],"date-time":"2016-03-31T09:28:52Z","timestamp":1459416532000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Icariin attenuates titanium-particle inhibition of bone formation by activating the Wnt\/\u03b2-catenin signaling pathway in vivo and in vitro"],"prefix":"10.1038","volume":"6","author":[{"given":"Junhua","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichuan","family":"Ping","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiexing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaozeng","family":"Xu","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":[[2016,3,31]]},"reference":[{"key":"BFsrep23827_CR1","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1038\/sj.gt.3302202","volume":"11","author":"PH Wooley","year":"2004","unstructured":"Wooley, P. 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