Anti-CD11b单克隆抗体对超高分子聚乙烯磨损颗粒诱导骨溶解作用的研究

摘要

Objective To investigate the effect of anti-CD1 1 b monoclonal antibody on bone dissolution model.Methods 32 10-week-old C57BL/6J female mice were divided into 4 groups with 8 in each group.Control group (A) received sham operation,then was given normal saline by gavage and received tail intravenous injection of PBS;Spleen tyrosine kinase(Syk) inhibitor group (B) received 20 μg Ultrahigh molecular weight polyethylene(UHMWPE) particles implantation onto the calvariae,then was given p505-15,15 mg/kg by gavage,and received tail intravenous injection of PBS;Anti-CD1 1 b antibody treatment group (C) received 20 μg UHMWPE particles implantation,then received tail intravenous injection of anti-CD11b antibody,2g/kg,and was given normal saline by gavage;Particle group (D) received 20 μg UHMWPE particles implantation,then was given normal saline by gavage and received tail intravenous injection of PBS.Two weeks later,the blood was used to measure TNF-α,and mouse calvariae were harvested for digital reconstruction using Micro-CT.The skull periostea were harvested for western blot.Results TNFαlevels of group A、B and C were lower than that of group D(P ＜0.05).Bone volume fraction(BVF) of group A、B and C were higher than that of group D(P ＜ 0.05).Erk activity,c-fos and NFATc1 of group B and C were lower than that of group D and higher than that of group A (P ＜ 0.05).Conclusion Anti-CD1 l b monoclonal antibody and Syk inhibitor can inhibit particles induced bone dissolution.CD1 1b can activate its downstream Syk pathway and promote osteoclast differentiation.%目的 通过建立小鼠颅骨溶解模型,探究anti-CD 11b抗体对颗粒诱导骨溶解的作用.方法 取10周龄雌性C57BL/6J小鼠32只,平均分为4组,A(空白对照组),切开颅顶皮肤后即缝合,于术后第二天灌胃生理盐水,并尾静脉注射PBS,B[脾酪氨酸激酶(Spleen tyrosine kinase,Syk)抑制剂组]、C(anti-CD 11b单克隆抗体组)和D(颗粒组)组于颅骨骨膜外移植20 μg超高分子聚乙烯磨损颗粒后缝合,B组术后第2大起以15 mg/kg灌胃Syk抑制剂,尾静脉注射PBS,C组术后第2天起尾静脉注射anti-CD11b单克隆抗体,2 g/kg,灌胃生理盐水,D组术后第二天起每日灌胃生理盐水,尾静脉注射PBS.两周后颈椎脱臼法处死小鼠,摘眼球取血测血清肿瘤坏死因子oα(tumor necrosis factor-α,TNF-αα)值,取颅骨做显微CT重建并测骨体积分数,取颅骨骨膜进行western blot分析.结果 建模小鼠全部存活,空白对照组、anti-CD11b单克隆抗体组及Syk抑制剂组血清TNF-d值均低于颗粒组(P＜0.05);空白对照组、anti-CD 11b单克隆抗体组与Syk抑制剂组骨体积分数均高于颗粒组(P ＜0.05);Syk抑制剂组及anti-CD11b单克隆抗体组Erk活性、c-fos及NFATc1表达均低于颗粒组而高于空白对照组(P＜0.05).结论 AntiCD11b单克隆抗体及Syk抑制剂均对颗粒诱导骨溶解具有抑制作用,CD11b分子通过激活Syk通路而发挥促破骨细胞分化作用.