Chen-He Zhou1,2,3, Zhong-Li Shi1,2, Jia-Hong Meng1,2, Bin Hu1,2, Chen-Chen Zhao1,2, Yu-Te Yang1,2, Wei Yu1,2, Ze-Xin Chen4, Boon Chin Heng5, Virginia-Jeni Akila Parkman3, Shuai Jiang6, Han-Xiao Zhu1,2, Hao-Bo Wu1,2, Wei-Liang Shen1,2, Shi-Gui Yan1,2. 1. Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. 2. Orthopedic Research Institute of Zhejiang University, Hangzhou, China. 3. Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA, USA. 4. Center of Clinical Epidemiology & Biostatistics, Department of Science and Education, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. 5. Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong. 6. Department of Hand Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, China.
Abstract
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 osteoclast formation, induced in vitro by the receptor activator of NF-κB ligand (RANKL). 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 signalling, specifically by targeting IκB kinases. 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 signalling by SPC was confirmed in vivo. CONCLUSION AND IMPLICATIONS: 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.
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 osteoclast formation, induced in vitro by the receptor activator of NF-κB ligand (RANKL). 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 signalling, specifically by targeting IκB kinases. 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 signalling by SPC was confirmed in vivo. CONCLUSION AND IMPLICATIONS: 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.
Authors: M A Lomaga; W C Yeh; I Sarosi; G S Duncan; C Furlonger; A Ho; S Morony; C Capparelli; G Van; S Kaufman; A van der Heiden; A Itie; A Wakeham; W Khoo; T Sasaki; Z Cao; J M Penninger; C J Paige; D L Lacey; C R Dunstan; W J Boyle; D V Goeddel; T W Mak Journal: Genes Dev Date: 1999-04-15 Impact factor: 11.361
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