Lithium chloride inhibits titanium particle-induced osteoclastogenesis by inhibiting the NF-κB pathway

// Xuanyang Hu 1, * , Zhirong Wang 2, * , Jiawei Shi 1, * , Xiaobin Guo 1, * , Liangliang Wang 1 , Zichuan Ping 1 , Yunxia Tao 1 , Huilin Yang 1 , Jun Zhou 1 , Yaozeng Xu 1 and Dechun Geng 1 1 Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, China 2 Department of Orthopedics, Zhang Jia Gang Hospital of Traditional Chinese Medicine, Zhangjiagang, China * These authors have contributed equally to this work Correspondence to: Jun Zhou, email: royf1@163.com Yaozeng Xu, email: xuyaozeng@163.com Dechun Geng, email: szgengdc@163.com Keywords: peri-implant osteolysis, wear debris, osteoclast, lithium chloride, NF-κB pathway Received: March 22, 2017      Accepted: July 19, 2017      Published: August 07, 2017 ABSTRACT Osteoclast over-activation and inflammation responses promote peri-implant osteolysis (PIO), which is the leading cause of aseptic artificial joint loosening. We examined the effect of lithium chloride (LiCl) on wear debris-induced osteoclastogenesis and inflammation. Fifty-Six C57BL/6J male mice were randomly distributed into four groups: sham control (sham, treated with phosphate buffered saline [PBS]), vehicle (treated with titanium/PBS), low-LiCl (L-LiCl, titanium: 50 mg/kg LiCl) and high-LiCl (H-LiCl, titanium: 200 mg/kg LiCl). After 14 days, mouse calvaria were harvested for micro-computed tomography and histomorphological and molecular analyses. Bone marrow-derived macrophages (BMMs) were extracted to examine osteoclast differentiation, and the RAW264.7 cell line was used to investigate osteoclastogenesis mechanisms. LiCl reduced the number of osteoclasts, debris-induced osteolysis, and the expression of inflammatory factors, thereby preventing bone loss in vivo . In vitro , LiCl inhibited osteoclastogenesis and osteoclastic bone resorption by inhibiting the RANKL-induced NF-κB signaling pathway. LiCl’s activation of the canonical Wnt/β-catenin signaling pathway was not associated with LiCl’s inhibition of osteoclastogenesis. These results suggest that LiCl may be an effective agent for treatment of osteolytic diseases caused by chronic inflammation and over-activation of osteoclasts.