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Extensive and over\u2010activated osteoclast formation and physiological functioning are regarded as the mechanism of prosthesis loosening. Therapeutic modalities based on inhibiting osteoclast formation and bone resorption have been confirmed to be an effective way of preventing aseptic prosthesis loosening. In this study, we have investigated the effects of sophocarpine (SPC, derived from<jats:styled-content style=\"fixed-case\"><jats:italic>Sophora flavescens<\/jats:italic><\/jats:styled-content>) on preventing implant loosening and further explored the underlying mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The effects of SPC in inhibiting osteoclastogenesis and bone resorption were evaluated in osteoclast formation, induced<jats:italic>in vitro<\/jats:italic>by the receptor activator of NF\u2010\u03baB ligand (RANKL). A rat femoral particle\u2010induced peri\u2010implant osteolysis model was established. Subsequently, micro\u2010CT, histology, mechanical testing and bone turnover were used to assess the effects of SPC in preventing implant loosening.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic>, we found that SPC suppressed osteoclast formation, bone resorption, F\u2010actin ring formation and osteoclast\u2010associated gene expression by inhibiting NF\u2010\u03baB signalling, specifically by targeting I\u03baB kinases. Our<jats:italic>in vivo<\/jats:italic>study showed that SPC prevented particle\u2010induced prosthesis loosening by inhibiting osteoclast formation, resulting in reduced periprosthetic bone loss, diminished pseudomembrane formation, improved bone\u2010implant contact, reduced bone resorption\u2010related turnover and enhanced stability of implants. Inhibition of NF\u2010\u03baB signalling by SPC was confirmed<jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>SPC can prevent implant loosening through inhibiting osteoclast formation and bone resorption. Thus, SPC might be a novel therapeutic agent to prevent prosthesis loosening and for osteolytic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14092","type":"journal-article","created":{"date-parts":[[2017,11,11]],"date-time":"2017-11-11T13:26:37Z","timestamp":1510406797000},"page":"859-876","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Sophocarpine attenuates wear particle\u2010induced implant loosening by inhibiting osteoclastogenesis and bone resorption<i>via<\/i>suppression of the NF\u2010\u03baB signalling pathway in a rat model"],"prefix":"10.1111","volume":"175","author":[{"given":"Chen\u2010he","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou China"},{"name":"Orthopedic Research Institute of Zhejiang University Hangzhou China"},{"name":"Department of Oral Medicine, Infection and Immunity Harvard School of Dental Medicine Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhong\u2010li","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou China"},{"name":"Orthopedic Research Institute of Zhejiang University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010hong","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou China"},{"name":"Orthopedic Research Institute of Zhejiang University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou China"},{"name":"Orthopedic Research Institute of Zhejiang University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen\u2010chen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou China"},{"name":"Orthopedic Research Institute of Zhejiang University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010te","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou China"},{"name":"Orthopedic Research Institute of Zhejiang University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou China"},{"name":"Orthopedic Research Institute of Zhejiang University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ze\u2010xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Center of Clinical Epidemiology &amp; 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