双膦酸盐对骨形成蛋白诱导骨骨吸收抑制作用的研究  

Effect of bisphosphonate YM175 inhibition on bone resorption of ectopic bone induced by bone morphogenetic protein 2

作　　者：宫琳[1] 唐伟华[1] 宫宁[2] 

机构地区：[1]北京航天中心医院口腔科,100039 [2]中国人民解放军总参316医院

出　　处：《中国骨质疏松杂志》2005年第2期236-238,155,共4页Chinese Journal of Osteoporosis

摘　　要：目的研究双膦酸盐(bisphosphonate YM 175)对骨形成蛋白(bone morphogenetic protein．简称BMP)诱导骨骨吸收的抑制作用。方法 42只大白鼠背部植入BMP,诱导出异位骨后,将大白鼠分成2组,即投药组和对照组。投药组在BMP植入后第3w至第7w,双膦酸盐(YM 175)每周投药3次,剂量1(μg／kg．d)。对照组按同样的方式给予等量的生理盐水。在BMP植入第3w、 4w、7w和10w,将BMP诱导骨取出,采用TRAP和cathepsin K染色方法来观察双膦酸盐对破骨细胞的作用。结果 BMP诱导骨3w时(即未投双膦酸盐药前),在BMP植入体周边形成编织骨 (woven bone),大量破骨细胞出现在新生骨组织表面。在4 w时,双膦酸盐投药组和对照组,新生骨组织均向BMP植入体内生长,但双膦酸盐投药组的破骨细胞较对照组有减少。在10 w时,双膦酸盐投药组和对照组均可观察到骨细胞变小并且有规律地排列的板层状骨(lamellar bone)的特征。而双膦酸盐投药组,破骨细胞死亡,与对照组比较,破骨细胞数目明显减少。结论双膦酸盐对破骨细胞性骨吸收有明显的抑制作用。Objective To determine the inhibited effects of bisphosphonate YM175 on bone resorption induced by bone morphogenetic protein (BMP) . Methods Ectopic bones were induced by recombi-nant human BMP-2 implanted subcutaneously on the back of 42 rats. Bisphosphonate YM175 1 μg/ kg. d was administered to the rats three times per week, from the 3rd to 7th week after implantation ( bisphosphonate group) . Aliquots of phosphate buffered saline were administered in the same protocol without bisphosphonate to the control group. On the end of 3rd, 4th, 7th or 10th week, the BMP-induced bones were removed and observed by enzyme histochemistry for tartrate-resistance acid phospha-tase (TRAP) and immunohistochemistry for cathepsin K. Results Before bisphosphonate being administered , woven bones had formed in the periphery of the BMP pellets, while osteoclasts were attached to these bones. At the end of 4th week, bone formation advanced to the implanted bones in both groups. But few osteoclasts were observed in the bisphosphonate group than that in the control at the 4 and 10 weeks. Both groups showed the characteristics of lamellar bones. Conclusions Osteoclast-mediated bone resorption was inhibited by the bisphosphonate administration.

关 键 词：双膦酸盐 骨形成蛋白 抑制作用 诱导骨 CATHEPSIN 破骨细胞性骨吸收 protein 新生骨组织 BMP 对照组 生理盐水 TRAP 染色方法 体内生长 细胞死亡 细胞数目 大白鼠 药组 异位骨 植入后 植入体 板层状 

分 类 号：R681[医药卫生—骨科学] R783.1[医药卫生—外科学]