Sophocarpine attenuates wear particle-
induced implant loosening by inhibiting
osteoclastogenesis and bone resorption via
suppression of the NF-κB signalling pathway
in a rat model
Shigui Yan and Wei-liang Shen, Department of Orthopedic Surgery, 2nd Afﬁliated Hospital, School of Medicine,
Zhejiang University, 88 Jie Fang Road, Hangzhou 310009, China. E-mail: firstname.lastname@example.org; email@example.com
3 March 2017;
31 October 2017;
6 November 2017
*, Zhong-li Shi
*, Jia-hong Meng
*, Bin Hu
, Boon Chin Heng
, Virginia-Jeni Akila Parkman
, Shuai Jiang
, Wei-liang Shen
and Shi-gui Yan
Department of Orthopedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China,
Institute of Zhejiang University, Hangzhou, China,
Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine,
Boston, MA, USA,
Center of Clinical Epidemiology & Biostatistics, Department of Science and Education, the Second Affiliated Hospital, School of
Medicine, Zhejiang University, Hangzhou, Zhejiang, China,
Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, and
Department of Hand Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, China
*C.Z, Z.S. and J.M contributed equally to this work.
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.
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
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 IκBkinases.Ourin vivo study showed that SPC prevented
particle-induced prosthesis loosening by inhibiting osteoclast formation, resulting in reduced periprosthetic bone loss, dimin-
ished 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.
British Journal of
British Journal of Pharmacology (2018) 175 859–876 859
DOI:10.1111/bph.14092© 2017 The British Pharmacological Society