Project/Area Number |
12832061
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Institution | Kanagawa Dental College |
Principal Investigator |
MIKUNI Yuko Kanagawa Dental College, Faculty of Dentistry, Lecturer, 歯学部, 講師 (60050689)
|
Co-Investigator(Kenkyū-buntansha) |
ITOMAN Moritoshi Kitasato University, Faculty of Medicine, Professor, 医学部, 教授 (70104528)
|
Project Period (FY) |
2000 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Keywords | osteocytes / ultrasound / osteopenia / disuse / synergy / mechanotransduction / bone formation / crosstalk |
Research Abstract |
In order to confirm our previous observation in isolated osteocytes of synergy between PTH and mechanical loading, in vivo, the 30-week-old female Wistar rats, either housed in cages of limited space (RESTRAINED and RESTRAINED+PTH) or allowed free activity (CONTROL and PTH) in the institutional standard cages, were inject subcutaneously with 10 μg/kg human PTH (1-34) or saline, three times a week. Rats were sacrificed after two sc calcein injections (6 mg/kg) 13 days and 3 days before death. For 3D evaluation, whole tibia was examined by pQCT and confocal laser microscopy. At the end of 6-week experiment, RESTRAINED and PTH is significantly different (p<0.001) and the differnce, was much larger than the added differences between RESTRAINED and CONTROL (not significant) and RESTRAINED and RESTRAINED+PTH (not significant). BMD of cortical bone also showed a significant difference between the RESTRAINED and PTH (p<0.001) in a similar manner. Also in confocal micrographs, larger numbers of much brighter periosteocytic calcein labels were obserbed in PTH compared to RESTRAINED suggesting the osteocytic mineralizing activity by combined effects of PTH and daily activity of rats. A critical role of osteocytes in sensitizing bone to PTH during daily activity was suggested. When PTH (1-34) alone or stretching alone exhibited moderate induction of mRNAs such as IGF-I or osteocalcin, we showed that stretch-loading in combination with PTH resulted in a dramatic upregulation.
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