Preventive Effect of YM175 on Steroid-induced Osteopenia in Rats

(1)泼尼松龙与YM 175合用对大鼠松质骨的影响7月龄雌性Wistar大鼠随机分为生理盐水对照组、泼尼松龙+溶媒组、泼尼松龙+YM 175低、高剂量组。PSL（2.5mg/kg/天）和YN 175（0.03或0.3mg/kg/天）同时皮下注射，每周6次，共8周。尸检时，采集双侧胫骨，并制备未脱钙Villanueva骨染色切片和脱钙TRAP染色切片。PSL+媒介物、PSL+ YM 175-低和-高组中的骨体积和骨形成相关参数低于对照组中的那些。在PSL+ YM 175-低和-高组中TRAP阳性表面和破骨细胞数量少于对照组中的那些。这些结果表明，同时给予PSL和YM 175降低了骨体积，并抑制了骨形成和骨吸收。我们在本研究中使用的YM 175剂量不能有效预防大鼠中类固醇诱导的骨质减少。(2)间歇性给予h-PTH（1-34）对泼尼松龙作用的MC 3 T3-E1细胞的影响。在<-6><-9>每48小时周期的前6小时，将具有10 μ M或10 μ M PSL的MC 3 T3-E1细胞暴露于h-PTH（1-34）。10 μ <-6>M和10 μ <-9>M PSL均能刺激ALP活性，但抑制蛋白含量，10 μ <-6>M PSL能刺激PTH/PTHrP受体mRNA的表达<-6>，h-PTH（1-34）与10 μ M <-6>PSL联合应用能刺激ALP活性，蛋白含量上级优于单独使用10 μ <-6>M PSL。这些结果表明，间歇性给予h-PTH（1-34）可刺激PSL抑制的成骨细胞的分化和恢复增殖。

(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.