Abstract:Objective To observe the effects of local injection of vascular endothelial growth factor(VEGF) and VEGF inhibitor bevacizumab on the wear debris-induced osteolysis by using mouse air pouch model,and to investigate the role of VEGF in aseptic loosening of artificial joints.Methods Forty mice were randomly divided into control group,particle group,VEGF group and VEGF inhibitor group,10 in each group.Air pouches were developed by hypodermic injection of sterile air into the back of mice,followed by implantation of bone grafts of calvaria from syngeneic mouse(n=10)donors.Mice in particle group,VEGF group and VEGF inhibitor group were given the injection of wear particles into air pouches.Mice in control group were given PBS.After bone implantation,recombinant human VEGF(rh-VEGF) and VEGF inhibitor bevacizumab were injected into air pouches in VEGF group and VEGF inhibitor group,respectively.Normal saline was injected into air pouches in particle group and control group.Pouch wall and implanted calvaria tissues were harvested 2 weeks after bone implantation for molecular and histological analysis.Inflammatory response and bone osteolysis were detected by HE staining,osteoclast differentiation and maturation by tartrate-resistant acid phosphatase staining,IL-1β and TNF-α concentrations by ELISA,and IL-1β and TNF-α expression by qRT-PCR.Results Compared with control group,wear particles significantly induced inflammatory response and bone osteolysis,and obviously increased the thickness of pouch wall,cell density and the expression of TNF-α and IL-1β(P<0.05).The injection of VEGF into the air pouches promoted the inflammatory response and bone osteolysis induced by wear particles,but the bevacizumab inhibited the role of wear particles.Conclusion Wear particles can induce VEGF expression in vivo,and VEGF inhibitor can effectively inhibit wear particle-induced inflammatory response and osteolysis.