| Project/Area Number |
14570747
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Okayama University |
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Principal Investigator |
INOUE Masaru Okayama University, Hospital, Lecturer, 医学部・歯学部附属病院, 講師 (20253023)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Hiroyuki Okayama University, Graduate School of Medicine and Dentistry, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80231413)
YAMANAKA Yoshitaka Okayama University, Hospital, Assistant, 医学部・歯学部附属病院, 助手 (60346442)
清野 佳紀 岡山大学, 大学院・医歯学総合研究科, 教授 (80028620)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | achondroplasia / PTH / FGFR3 / bone growth / 軟骨細胞 / アポトーシス / FGF receptor 3 / STAT1 / 骨成長障害 / Stat1 |
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| Research Abstract |
Achondroplasia (ACH) is the most common form of genetic short statue. Recently we treat them with human growth hormone but its effect is limited. To explore new therapeutic applications, we performed PTH treatment for ACH model mouse (AchTG).
[Short-term-trial] Wild (WT) and AchTG were treated with daily PTH subcutaneous injection (100μ/kg,1000μ/kg or vehicle) during day 7 to 20, then at day 21, their femurs were dissected, measured their length and analyzed histologically. [Long-term-trial] WT and AchTG mouse were treated with 3-times/week PTH subcutaneous injection (100μ/kg) during 1^<st> to 5^<th> week, then at day 42, their femurs, tibias, radiuses and humeruses were dissected, measured their length and analyzed histologically.
AchTG femurs were significantly disturbed in longitudinal bone growth compared with WT ones. PTH significantly improved bone growth of AchTG but of WT. Histologically, PTH expands growth plate in both AchTG and WT femurs in short-term-trial but in long-term-trial.
We confirmed that constitutive active FGFR3 mutation suppressed bone growth in transgenic mice and that PTH rescued bone from the growth disturbance. Our results suggest that PTH has potential to rescue the bone growth disturbance in achondroplasia.
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