The Study Of The Role Of Vascular Endothelial Growth Factor In Wear Particles-induced Osteolysis

ObjectiverTo establish the Bone implant in air pouch mouse model of wear particle-induced osteolysis and observe the effect of local injection of VEGF and VEGF inhibitor bevacizumab on the wear particle-induced aseptic inflammation and osteolysis,and then investigate its significance in the process of aseptic loosening of Artificial joints.Methods:50female kunming strain mice (aged8-10weeks, weighted25g) were selected.10mice as the donor of bone graft, the other40mice were equally divided into control group (groups A), particle group (group B), VEGF group(group C), and VEGF inhibited group(group D). Air pouches were established on the back of40mice by injection3ml sterile air subcutaneously firstly and the air pouches were added with1ml of air on alternate days.On day8, a graft of calvaria from the donor mice were implanted in air pouches. In group B,group C and group D,0.5ml wear particles suspension was injected into the air pouches, in group A, PBS was used. After bone implantation,in group C and group D,Recombinant human VEGF (rh-VEGF) and VEGF inhibitor (bevacizumab) were injected into the air pouches respectively.In group B and group A,saline was used.Pouch tissues and bone were harvested2weeks after bone implantation to HE staining, qRT-PCR and ELISA analyses.Results:All mice survived to the end of experiment.The gross observation showed that the red,swollen and vascular proliferation of air pouches were slight in group A, and were most obvious in group C. group B second to group C,and group D were situated between group A and group B.The histological and molecular biological analysis showed that inflammatory reaction and osteolysis were significantly in group B and the thickness of pouch,cell density and the expression of imflammtory cytokine included TNF-α、IL-1β was significantly higher than group A(P<0.05). The inflammatory reaction and bone osteolysis were most significantly in group C and The above-mentioned index were higher then group B(P<0.05). There are some inflammatory reaction and osteolysis in group D, but lower than group B (P< 0.05)and higher than group A(P<0.05).Conclusion:wear particles could induced VEGF expression in vivo, and it may play an promoting role in The aseptic loosening of Artificial joints.VEGF antibody bevacizumab can effectively inhibit wear particle-induced inflammatory reaction and osteolysis.