Project/Area Number |
07671563
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | AKITA UNIVERSITY |
Principal Investigator |
SATO Kozo Orthopedic Department of Akita University, School of Medicine, Professor, 医学部, 教授 (50004875)
|
Co-Investigator(Kenkyū-buntansha) |
OKADA Kyoji Orthopedic Department of Akita University, School of Medicine, Assistant Lecture, 医学部, 助手 (10185431)
|
Project Period (FY) |
1995 – 1996
|
Project Status |
Completed (Fiscal Year 1996)
|
Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
|
Keywords | steroid-induced osteopenia / bisphosphonate / YM-175 / parathyroid hormone / bone histomorphometry / Parathyroid hormone / ステロイド / MC3T3-E1 / PTH / PTHrP受容体 / ステロイド性骨減少症 / YM175 / 予防効果 |
Research Abstract |
(1) Effects of concurrent administration of prednisolone and YM175 on cancellous bone in rats Seven-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.
|