Preventive Effect of YM175 on Steroid-induced Osteopenia in Rats

(1)强的松龙和YM175同时给药对大鼠松质骨的影响将7月龄雌性Wistar大鼠分为生理盐水对照组、强的松龙+载药组、PSL+YM175- low和-High组。PSL （2.5mg/kg/d）和YN175（0.03或0.3mg/kg/d）同时皮下给药，每周6次，连续8周。尸检时，采集双侧胫骨，制作未钙化Villanueva骨染色切片和脱钙化trap染色切片。PSL+vehicle组、PSL+YM175-Low组和-High组骨体积及骨形成相关参数均低于对照组。PSL+YM175-Low和high组的trap阳性表面和破骨细胞数量均少于对照组。上述结果表明，PSL和YM175同时给药可减少骨体积，抑制骨形成和骨吸收。本研究使用的YM175剂量对大鼠激素性骨质减少无明显预防作用。(2)间歇性给药h-PTH（1-34）对强的松龙暴露的MC3T3-E1细胞的影响。PSL浓度为10^<-6>M或10^<-9>M的MC3T3-E1细胞在每48小时周期的前6小时暴露于h-PTH（1-34）。10^<-6>M和10^<-9>M可刺激ALP活性，而10^<-6>M可抑制蛋白质含量。PSL的10^<-6>M可刺激PTH/PTHrP受体mRNA的表达，h-PTH（1-34）与PSL的10^<-6>M联合可刺激ALP活性和蛋白含量优于单独使用PSL的10^<-6>M。这些结果表明，间歇性给药h-PTH（1-34）可刺激PSL抑制的成骨细胞分化并恢复其增殖。

(1) Effects of concurrent administration of prednisolone and YM175 on cancellous bone in ratsSeven-month-old female Wistar rats were divided into following four groups : saline administrated control group, PSL (prednisolone) +vehicle group, PSL+YM175-Low and -High group. PSL (2.5mg/kg/day) and YN175 (0.03 or 0.3mg/kg/day) were concurrently administrated subcutaneously, 6 times a week for 8 weeks. At necropsy, bilateral tibiae were collected and prepared with undecalcified Villanueva bone staining sections and decalcified TRAP-staining sections. The bone volume and bone formation related parameters in PSL+vehicle, PSL+YM175-Low and -High groups were lower than those in the control group. TRAP-positive surface and osteoclast number in the PSL+YM175-Low and-High groups were less than those in the control group. These results show that concurrent administration of PSL and YM175 decreased bone volume, and restrained both bone formation and resorption. The dosages of YM175 which we used in this study were not effective to prevent steroid-induced osteopenia in rats.(2) Effects of intermittent administration of h-PTH (1-34) on MC3T3-E1 cells exposed to prednisolone.MC3T3-E1 cells with 10^<-6>M or 10^<-9>M of PSL were exposed to h-PTH (1-34) for the first 6hr in every 48hr-cycle. ALP activity was stimulated by 10^<-6>M and 10^<-9>M of PSL,but protein content was inhibited by 10^<-6>M of PSL.Expression of PTH/PTHrP receptor mRNA was stimulated by 10^<-6>M of PSL.h-PTH (1-34) combined with 10^<-6>M of PSL stimulated ALP activity and protein content superior to 10^<-6>M of PSL only. These results suggest that intermittent administration of h-PTH (1-34) stimulate the differentiation and recover the proliferation of osteoblast suppressed by PSL.