The Effect Of Celastrol On Osteoclastogenesis And Reduction Of Titaniumparticle-induced Osteolysis Via Suppression Of NF-?B And MAPK Signaling Pathway

Objective:The aim of this study was to assess the effect of Celastrol on osteoclastogenesis and titanium particle induced osteolysis.Methods:In vitro experiments:Add Celastrol to RAW264.7 cells and observe the effect of it during the time of osteoclast formation.Mainly include: a.CCK-8 method to clarify the range of toxicity of Cel on RAW264.7 cells;b.To study the effect of Cel on osteoclasts;c.To study the effect of Cel on osteoclast differentiation-related genes;d.To explore the effect of Cel on osteoclast signaling pathway;In vivo experiment:Observe the effect of different concentrations of Cel on mouse models.Results:1.In vitro experiments:a.Cel is non-toxic to RAW264.7 cells within 200 nM;b.Cel has a strong inhibitory effect on osteoclast formation,and this inhibition is positively correlated with drug concentration;c.Cel can effectively inhibit osteoclast related gene resistance TRAP,Ctsk,V-ATPase a3,V-ATPase d2,c-fos,and NFATC1expression;d.Cel can inhibit the two pathways of NF-?B and MAPK,then affect the expression of c-fos,c-jun and NFATC1,and finally inhibit the formation of osteoclasts;2.In vivo experiment:Wear particles cause a strong osteolysis effect,high concentration of Cel inhibits osteolysis and protects calvarial bone from osteolysis.Conclusion:In vitro Cel can inhibit NF-?B and MAPK pathways to inhibit osteoclasts in non-toxic concentrations,and then reduce osteoclast specific gene expression.In vivo Cel can protect mouse bone surface from damage by wear particles.Finally,it plays a role in preventing the aseptic loosening of artificial joints.