BM_(210955)抗骨吸收细胞药效与作用机制

Inhibitory Effect and Cell Mechanism of BM_(210955) on Bone Resorption

目的 研究BM2 10 955延缓骨量丢失、抑制骨吸收的细胞药效和作用机制。方法 由 10日龄新西兰兔四肢长骨分离破骨细胞接种于象牙片和盖玻片上培养 ,应用TRAP(抗酒石酸酸性磷酸酶 )、TB(甲苯胺蓝 )和吖啶橙荧光染色等技术 ,观察不同浓度BM2 10 955药物对破骨细胞生存率、骨吸收功能和凋亡率等细胞药效评价指标的影响。结果 BM2 10 955降低TRAP(+)多核细胞数目 ,10 -8mol/L组较对照组减少 73% ;BM2 10 955抑制骨片吸收陷窝的形成 ,作用强度与药物浓度有关 ,10 -12 、10 -10 和 10 -8mol/L组抑制率分别为 31.5 8%、76 .32 %和87.99% ;10 -8mol/L以上药物浓度对破骨细胞凋亡有诱导作用 ,10 -4 mol/L组凋亡指数为 6 2 %。结论 诱导破骨细胞凋亡、降低破骨细胞生存数目并抑制细胞的骨吸收功能是BM2 10 955延缓骨丢失、抑制骨吸收的主要机制之一。

Purpose To investigate the mechanism of BM 210955 (ibandronate,a new bisphosphonate drug manufactured in China)in the prevention of bone loss in vitro . Methods The osteoclasts isolated from the long bone of 10 day old Rabbit were cultured on glass and bone slices in different concentration of BM 210955 .TRAP(tartrate resistant acid phosphonase) staining for osteoclast and TB(toluidine blue)staining for resorption lacunae were used on bone slices and Fluorescence (orange acridine) staining for apoptosis cell on glass slices was used;Multinucleated(three and more nuclei) TRAP positive cell and Apoptosis cell and Pits were counted. Results The BM 210955 decreased the multinucleated cell number by 73% in 10 -8 mol/L;The inhibitory rate of pit formed was correlate to concentration as 31.58%,76.32% and 87.99%to 10 -12 ,10 -10 and 10 -8 mol/L;The apoptosis induction was shown in above 10 -8 mol/L,and the apoptosis rate was 62% in 10 -4 mol/L. Conclusions Induction of osteoclast apoptosis and decrease of the cell number and inhibition of resorptive ability were the major mechanism for bone loss prevention effect of BM 210955 in vitro .