[Inhibitory effects of vascular endothelial growth factor antibody on wear particle-induced osteolysis].
OBJECTIVE
To observe the effect of local injection of vascular endothelial growth factor (VEGF) and VEGF antibody on the wear particle-induced osteolysis in the mouse air pouch model and to investigate the role of VEGF in the process of aseptic loosening of prosthesis.


METHODS
The stem of metal hip prosthesis was obtained from the revision surgery. Metallic wear particles were made by vacuum ball milling. Wear particles suspension was prepared into the concentration of 10 mg/mL with PBS. Fifty female Kunming mice (aged 8-10 weeks, weighing about 25 g) were selected. Of 50 mice, 10 were used as the donors of bone graft, the other 40 were equally divided into control group (group A), particle group (group B), VEGF group (group C), and VEGF inhibited group (group D). Air pouches were made on the back of 40 mice by injecting sterile air subcutaneously. At 8th day, a graft of calvaria from the donor mice was implanted in air pouch. In groups B, C, and D, 0.5 mL wear particles suspension was injected into the air pouches, and in group A, 0.5 mL PBS was injected. Once a day at 6th and 7th days during the air pouch preparation and one time every two days after bone implantation, 0.2 mL recombinant human VEGF (rhVEGF) and VEGF antibody (Bevacizumab) were injected into the air pouches in groups C and D, respectively. In group A and group B, 0.2 mL saline was injected. Pouch tissues and bone were harvested at 2 weeks after bone implantation for HE staining, real-time fluorescent quantitative PCR and ELISA analyses.


RESULTS
All mice survived to the end of experiment. The gross observation showed that there were mild redness, swelling, and less neovascularization in air pouches in group A. There were obvious redness, swelling, and more exudative and neovascularization in groups B, C, and D, most obvious in group C, the next in group B, then in group D. The histological and molecular biological analysis showed that inflammatory responses and osteolysis were obvious in group B and the pouch membrane thickness, the cell density, transforming growth factor alpha, interleukin 1beta, and VEGF were significantly higher than those in group A (P < 0.05). The inflammatory responses and osteolysis were most obvious in group C and the above-mentioned indexes were significantly higher than those in group B (P < 0.05). There were some inflammatory responses and osteolysis in group D, but the indexes were significantly lower than those in group B (P < 0.05) and were significantly higher than those in group A (P < 0.05).


CONCLUSIONS
VEGF can promote inflammatory responses and osteolysis in aseptic loosening of prosthesis. VEGF antibody can effectively inhibit wear particle-induced osteolysis.
Department of Orthopedics, the First Affiliated Hospital of Nanchang University, Nanchang Jiangxi, 330006, P.R.China. daimin@medmail.com.cn
Min
M
Dai
Yanchun
Y
Zhong
Ling
L
Zong
Xiaogang
X
Yang
Ming
M
Cheng
Kanghua
K
Yang
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D016025:Bone Transplantation; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D007595:Joint Prosthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010014:Osteolysis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011475:Prosthesis Failure; D011897:Random Allocation; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000276:immunology
D061067:Antibodies, Monoclonal, Humanized; D053583:Interleukin-1beta; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A