Research About Effects Of Celastrol On Prevention Of Wear Particle-induced Osteolysis

Objective:Through investigate the effects of different doses and cell culture concentration of celastrol on osteolysis induced by titanium particles and osteoclasts.We purposed to provide theoretical basis for the further application of celastrol to prevent periprosthetic osteolysis induced by wear particles.Methods:In vitro,we via CCK-8 to determine the cytotoxicity of celastrol on monocytemacrophage derived from mouse BMMs.Then the effect of different concentrations of celastrol on osteoclastogenesis were observed.In vivo,20 male C57BL/6J 6-week old mice were randomly divided into four groups with 5 mice in each group: sham group with saline,vehicle group,wear particles +(1 mg/kg)low dose celastrol group and titanium particles +(3 mg/kg)high dose celastrol group.The mouse calvaria osteolysis model induced by wear particles were established and injected celastrol intraperitoneally at a dose of 3 mg / kg(high dose group)and 1 mg / kg(low dose group)respectively.All mice were sacrificed and tissue specimens were acquired at 2weeks after operation.Micro-computed tomography,hematoxylin-eosin staining were applied for the pathological investigation of calvaria.ELISA were employed to analysis the expression of TRAP5 b and CTX-Ⅰ in the serum.Results:During the experiment,the survival of mice and the vivability of osteoclasts precursor didn’t influenced by celastrol.In vitro,we found that celastrol can significantly inhibit the process of mouse BMMs derived mononuclear-macrophages differentiate into osteoclast.In the group treated with high-dose celastrol,wear particle-induced osteolysis were significantly reduced compared with that in the vehicle-treated control.Moreover,group treated with high-dose celastrol suppressed the wear particle-induced osteolysis were displayed on the increased BMD(Bone Mineral Density)and BVF(Bone Volume Fraction),and decreased the percentage ofporosity.Moreover,the concentration of TRAP5 b and CTX-Ⅰin serum were accordance with these result.Over all,Compared with vehicle group,osteolysis were relieved in the celastrol-treated group.Conclusion:Celastrol can inhibit the process of mouse BMMs derived mononuclearmacrophages differentiate into osteoclast in the range of nontoxic concentration;artificial joint wear debris can induce a mouse cranium osteolysis model sucessfully;Celastrol can effectively relief prosthesis wear partile-induced mouse cranium osteolysis.