| Project/Area Number |
16390303
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
TANAKA Hiroyuki (2005-2006) Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, associate professor, 大学院医歯薬学総合研究科, 助教授 (80231413)
山中 良孝 (2004) 岡山大学, 医学部・歯学部附属病院, 助手 (60346442)
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| Co-Investigator(Kenkyū-buntansha) |
NONOMIYA Shinsuke Okayama University Hospital, assistant professor, 医学部・歯学部附属病院, 講師 (10325110)
田中 弘之 岡山大学, 大学院・医歯学総合研究科, 助教授 (80231413)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥9,100,000 (Direct Cost: ¥9,100,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Achondroplasia / FGFR3 / chondrocytes / hone organ culture / transgenic mouse / PTH / BiP / HMGB1 / 副甲状腺ホルモン / BiP / TDII / 変異 / 骨伸長 / 線維芽細胞成長因子受容体3 / リガンド依存性 / PLCγ / FGF recetor 3 / STAT1 / 骨成長障害 |
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| Research Abstract |
To explore molecular mechanisms of bone growth, we analyzed intracellular signal transduction in achondroplastic chondrocyte as a model of bone growth failure, in which the causative factor was already identified as mutations in fibroblast growth factor receptor 3 gene. We already have identified that parathyroid hormone (PTH) is a key factor for a new treatment of the short stature in achondroplasia from mainly in vitro experiments. Therefore, we at first examine the effects of recombinant human PTH on bone organ culture and mutated FGFR3 overexpressed transgenic mouse(ACH-TG). In organ culture system, excised bones from 19 PCD fetus were cultivated with or without PTH fro 4-days. In this system, PTH clearly stimulated accumulation of cartilage in both ends and bone lengthening. In ACH-TG, 5weeks treatment with 10Oug/kg of PTH clearly stimulated bone growth of ACH-TG. From these results, we concluded that PTH is one of the promising agents for the treatment of Achondroplasia.
To clarify abnormal signal transduction induced by mutated FGFR3, we performed proteomics approach. We screened proteins which may associate with mutated FGFR3 specifically. Proteomics approach identified two specifically associate proteins, BiP and HMGB1.Following experiments showed that BiP is important signal for the retention of mutated FGFR3 in endoplasmic reticulum and that HMGB1 may play an important roles in defective cell growth in achondroplasia.
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