Sophocarpine attenuates wear particle-induced implant loosening by inhibiting osteoclastogenesis and bone resorptionviasuppression of the NF-κB signalling pathway in a rat model

Autor:	Chen-chen Zhao, Virginia-Jeni Akila Parkman, Ze-xin Chen, Boon Chin Heng, Han-Xiao Zhu, Shuai Jiang, Weiliang Shen, Jiahong Meng, Haobo Wu, Bin Hu, Shigui Yan, Chen-he Zhou, Wei Yu, Yute Yang, Zhongli Shi
Rok vydání:	2018
Předmět:	musculoskeletal diseases 0301 basic medicine Pharmacology Osteolysis Chemistry fungi Periprosthetic NF-κB medicine.disease Bone resorption Bone remodeling 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology medicine.anatomical_structure In vivo Osteoclast medicine Cancer research Implant
Zdroj:	British Journal of Pharmacology. 175:859-876
ISSN:	0007-1188
DOI:	10.1111/bph.14092
Popis:	Background and Purpose Aseptic prosthesis loosening, caused by wear particles, is one of the most common causes of arthroplasty failure. Extensive and over-activated 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 Sophora flavescens) on preventing implant loosening and further explored the underlying mechanisms. Experimental Approach The effects of SPC in inhibiting osteoclastogenesis and bone resorption were evaluated in RANKL-induced osteoclast formation in vitro. A rat femoral particle-induced peri-implant osteolysis model was established. Subsequently, micro-CT, histology, mechanical testing and bone turnover were used to assess the effects of SPC in preventing implant loosening. Key Results In vitro, we found that SPC suppressed osteoclast formation, bone resorption, F-actin ring formation and osteoclast-associated gene expression by inhibiting NF-κB signaling, specifically by targeting IκB kinases (IKKs). Our in vivo study showed that SPC prevented particle-induced prosthesis loosening by inhibiting osteoclast formation, resulting in reduced periprosthetic bone loss, diminished pseudomembrane formation, improved bone-implant contact, reduced bone resorption-related turnover, and enhanced stability of implants. Inhibition of NF-κB signaling by SPC was further confirmed in vivo. Conclusion and Implications Our data demonstrated that 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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::7531b9233d74172ac4c86cf32548494f https://doi.org/10.1111/bph.14092 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.