P60PLAD蛋白对超高分子量聚乙烯(UHMWPE)颗粒诱导的小鼠颅盖骨骨溶解模型以及小鼠卵巢切除骨质疏松模型的影响  

Effects of P60PLAD on Ultra High Molecular Weight Polyethylene(UHMWPE)-induced Osteolysis and OVX-induced Osteoporosis in Mice

作　　者：闫昭[1] 朱锦宇[1] 吴海宁[1] 孙孟帅 朱庆生[1] 曹晓瑞[1] 

机构地区：[1]第四军医大学西京医院全军骨科研究所,陕西西安710032

出　　处：《现代生物医学进展》2017年第5期839-843,855,共6页Progress in Modern Biomedicine

基　　金：陕西省自然科学基础研究计划项目(2014JQ4142)

摘　　要：目的:构建UHMWPE颗粒诱导的小鼠颅盖骨骨溶解模型以及小鼠卵巢切除骨质疏松模型,通过动物模型证实P60PLAD蛋白在体内具有破骨细胞抑制特性和骨保护作用。方法:用8周C57BL/6雄性小鼠实验。在小鼠颅盖骨沿正中线做一矢状切口,暴露0.5 cm×0.5 cm范围,保证骨膜完整性,将直径在0.1-10μm的超高分子量聚乙烯(Ultra High Molecular Weight Polyethylene)颗粒20μg均匀撒在骨膜,构建小鼠颅盖骨骨溶解模型,在局部注射PBS或者P60PLAD蛋白溶液。2周后处死,将颅骨分离进行Micro-CT检查比较骨溶解区域变化。手术切除10周雌性小鼠卵巢构建小鼠去卵巢骨质疏松模型,腹腔注射PBS或P60PLAD蛋白溶液。12周后处死后分离股骨,经4%多聚甲醛固定后行Micro-CT检查比较骨密度等参数。结果:超高分子量聚乙烯(Ultra High Molecular Weight Polyethylene)颗粒诱导的骨溶解模型中,加入P60PLAD蛋白后,颅骨局部骨溶解区域较对照组减少,骨量相关参数与对照组相比有统计学意义。在小鼠卵巢切除骨质疏松模型中,注射了P60PLAD蛋白的实验组,其骨密度(BMD)等与骨量相关参数较对照组有明显增加。结论:P60PLAD蛋白可有效抑制UHMWPE颗粒诱导的小鼠颅盖骨骨吸收模型局部的骨吸收,抑制局部破骨细胞的骨吸收作用,并可以部分逆转小鼠卵巢切除骨质疏松模型的骨质疏松,提高骨密度,在破骨细胞抑制活性和骨保护方面具有良好临床应用前景。Objective： To establish UHMWPE particle-induced calvarial osteolysis murine model and ovariectomized mouse model,and observe the effects of P60 PLAD on osteoclastogenesis, differentiation of osteoclast and bone resorption, as well as the bone protection property. Methods： 8-week C57BL/6 male mice were utilized to establish the model. A 0.5 cm ×0.5 cm area of calvarial bone was exposed by making a midline sagittal incision over the calvaria, leaving the periosteum intact. Distribute 20 μg UHMWPE particles the diameter of which ranged from 0.1 to 10 μm over the the intact periosteum to establish the UHMWPE particle-induced calvarial osteolysis murine model. Mice were provided PBS or p60 PLAD solution after surgery locally. After 2 weeks, all mice were sacrificed and skulls were separated to undergo Micro-CT to observe the changes in osteolysis area. Ovariectomy was performed on 10-week-old female C57BL/6 mice to establish the ovariectomized mouse model. All mice were intraperitoneally injected with PBS or P60 PLAD solution for12 weeks. After 12 weeks, all mice were sacrificed and femora were separated and fixed in 4% paraformaldehyde for Micro-CT. Results：There was significant difference in the bone resorption pits between P60 PLAD protein group and the control group. When P60 PLAD solution was used, area of bone resorption greatly decreased in comparison with the control group. Bone mass quantified analysis confirmed the bone protection effect in P60 PLAD group. For the OVX mouse model, BMD and other parameters indicating bone quantity and quality increased greatly in P60 PLAD group compared with the control group. Conclusion： P60 PLAD protein could efficiently suppress the UHMWPE-induced osteolysis as well as the osteoclastic bone resorption in murine model. P60 PLAD treatment significantly alleviated osteoporosis in OVX mouse model. On the basis of our previous research work, P60 PLAD had a good prospect of clinical application in the respects of suppressing osteoclastic bone resorption and bone prote

关 键 词：P60PLAD蛋白 破骨细胞 骨吸收 骨溶解 

分 类 号：R-33[医药卫生] R68