Inhibition Effect And Mechanism Of Farrerol On Osteoclast Differentiation And Aseptic Loosening Of Prosthesis

Objective: To investigate the inhibitory effect of Farrerol on osteoclast differentiation and bone resorption induced by Titanium(Ti)particles,and to explore its mechanism.Methods: The safe concentration of Farrerol was screened by CCK-8method.TRAP staining was used to observe the effects of Farrerol on osteoclast differentiation.Quantitative polymerase chain reaction(q PCR)was used to detect the effect of Farrerol on osteoclast specific gene expression.The Ti particle induced osteolysis model of mouse skull was established to detect the inhibitory effect of Farrerol on Ti particle induced osteolysis.The possible signaling pathways of rhododendron inhibiting osteoclast differentiation and bone resorption were predicted by network pharmacology.Western Blot(WB)experiment was used to verified the effect of Farrerol on osteoclast signal pathway and its mechanism.Results: Farrerol did not significantly inhibit the proliferation of Raw264.7 cells and bone marrow macrophages(BMMs)in mice at concentration of 50μM and below concentration.Farrerol could inhibit the osteoclast differentiation of RAW264.7 cells and BMMs cells induced by RANKL.Farrerol inhibited m RNA expression of osteoclast specific genes(Nfatc1,Ctr,Trap,C-FOS,V-ATPAS-D2 and Cathepsin K)in vitro.Farrerol can reduce Ti particle induced skull osteolysis in mice.Farrerol inhibited RANKL induced NF-κB degradation and ERK phosphorylation.Conclusion: Farrerol inhibits osteoclast differentiation and Ti particle induced bone resorption by inhibiting the RANKL induced NF-κB degradation and ERK phosphorylation.