The Study Of Lithium Chloride Inhibiting Wear Paticles-induced Inflammatory Osteolysis

Osteoclast and inflammation responses are the key factors for peri-implant osteolysis(PIO),which is leading cause of aseptic loosening.In present study,our aim was to explore effect of Lithium chloride(LiCl)on wear debris-induced osteoclastogensis and inflammation.Fifty-six C57BL/6J male mice were distributed into four groups randomly: sham control(sham,treated with phosphate buffered saline [PBS]),vehicle(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,we collected the mouse skull and analyzed the information of the skull osteolysis in mice by microcomputer tomography,histomorphological staining and immunohistochemical staining.The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay(Elisa).Meanwhile,Bone-marrow-derived macrophages(BMM)were extracted to examine the effect of LiCl on osteoclast differentiation and function,and RAW264.7 cell line were used to investigate underlying mechanism of LiCl regulating osteoclastogensis.LiCl markedly alleviated the severity of wear debris-induced osteolysis,reduced the expression of inflammatory factors and osteoclast number and thus prevented bone loss in vivo.Besides,the results in vitro indicated LiCl inhibited osteoclastogensis and osteoclastic bone resorption mainly via regulating RANKL-induced NF-κB signaling pathway.Meanwhile,as an seletive inhibitor of glycogen synthetase kinase 3 beta(GSK-3β),the activation of the canonical Wnt signaling by LiCl are not associated with osteoclastogensis.Collectively,these results suggested LiCl,originally used as treatment for the patients with mental diseases,may develop to be an effective agent for osteolystic diseases caused by chronic inflammation and over-activation of osteoclast.