| Project/Area Number |
17590958
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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 |
Endocrinology
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| Research Institution | Kyoto University |
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Principal Investigator |
KOMATSU Yasato Kyoto University・Graduate School of Medicine, part time lecturer, 医学研究科, 非常勤講師 (40322648)
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| Co-Investigator(Kenkyū-buntansha) |
YASODA Akihiro Kyoto University・Graduate School of Medicine, assistant professor, 医学研究科, 助手 (50378642)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | natriuretic peptide / guanylyl cyclase / endochondral ossification / achondroplasia / growth factor / 四肢短縮型小人症 / 遺伝子改変動物 |
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| Research Abstract |
It is well known that natriuretic peptide family is an important cardiovascular regulator, and ANP and BNP are clinically used as biochemical markers and drugs for heart failure. Recently we have elucidated that another member of natriuretic peptides, CNP, is a strong stimulator of bone growth. In this project, we performed translational research for the stimulating effect of CNP on endochondral bone growth. At first we generated CNP-transgenic mice under the control of human serum amyloid P component promoter (SAP), which enables elevation of plasma concentration of CNP, as mice model of CNP administration (SAP-CNP-Tg mice). SAP-CNP Tg mice exhibit widened growth plate and according skeletal overgrowth. In order to confirm the effect of circulating CNP in SAP-CNP Tg mice, we tried to rescue impaired skeletal growth of CNP knockout mice by cross-mating CNP knockout mice with SAP-CNP Tg mice. The shortening of bones in CNP knockout mice formed through endochondral ossification was greatly recovered in the resultant SAP-CNP-Tg/CNP knockout mice. Histological analysis revealed that narrowed growth plates in CNP knockout mice were greatly recovered in SAP-CNP-Tg/CNP knockout mice. Next we tried exogenous administration of synthesized CNP to wild type mice and confirmed the effect on bone growth. Exogenous administration of CNP elongated bones formed through endochondral ossification just like SAP-CNP-Tg mice. We are planning more close analysis on CNP administration to mice, with the aim of clinical use of CNP against skeletal dysplasias, diseases in which growth of bones are impaired.
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