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2006 Fiscal Year Final Research Report Summary

Translational research of C-type natriuretic peptide as an stimulator of endochondral bone growth

Research Project

Project/Area Number 17590958
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionKyoto University

Principal Investigator

KOMATSU Yasato  Kyoto University・Graduate School of Medicine, part time lecturer, 医学研究科, 非常勤講師 (40322648)

Co-Investigator(Kenkyū-buntansha) YASODA Akihiro  Kyoto University・Graduate School of Medicine, assistant professor, 医学研究科, 助手 (50378642)
Project Period (FY) 2005 – 2006
Keywordsnatriuretic peptide / guanylyl cyclase / endochondral ossification / achondroplasia / growth factor
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.

  • Research Products

    (14 results)

All 2006 2005

All Journal Article (14 results)

  • [Journal Article] Interferon-a improves bone resorption and osteopenia in patients with chronic hepatitis C.2006

    • Author(s)
      Nishida N, Komatsu Y, Komeda T, Fukuda Y
    • Journal Title

      Hepatology Res. 34

      Pages: 222-227

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Clinical significance of risedronate for osteoporosis in the initial treatment of male patients with Graves' disease.2006

    • Author(s)
      Majima T, Komatsu Y, Doi K, Takagi C, Shigemoto M, Fukao A, Morimoto T, Corners J, Nakao K
    • Journal Title

      J Bone Miner Metab. 24

      Pages: 105-113

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Safety and efficacy of low-dose pioglitazone (7.5 mg/day) vs. standard-dose pioglitazone (15 mg/day) in japanese women with type 2 diabetes mellitus.2006

    • Author(s)
      Majima T, Komatsu Y, Doi K, Shigemoto M, Takagi C, Fukao A, Corners J, Nakao K
    • Journal Title

      Endocr J. 53

      Pages: 325-330

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Negative correlation between bone mineral density and TSH receptor antibodies in male patients with untreated Graves' disease.2006

    • Author(s)
      Majima T, Komatsu Y, Doi K, Takagi C, Shigemoto M, Fukao A, Morimoto T, Corners J, Nakao K
    • Journal Title

      Osteoporos Int. 17

      Pages: 1103-1110

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Interferon-α improves bone resorption and osteopenia in patients with chronic hepatitis C.2006

    • Author(s)
      Nishida N, Komatsu Y, Komeda T, Fukuda Y
    • Journal Title

      Hepatology Res. 34

      Pages: 222-227

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Clinical significance of risedronate for osteoporosis in the initial treatment of male patients with Graves' disease.2006

    • Author(s)
      Majima T, Komatsu Y, Doi K, Takagi C, Shigemoto M, Fukao A, Morimoto T, Corners J, Nakao K.
    • Journal Title

      J Bone Miner Metab. 24

      Pages: 105-113

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Safety and efficacy of low-dose pioglitazone (7.5 mg/day) vs. standard-dose pioglitazone (15 mg/day) in japanese women with type 2 diabetes mellitus.2006

    • Author(s)
      Majima T, Komatsu Y, Doi K, Shigemoto M, Takagi C, Fukao A, Corners J, Nakao K.
    • Journal Title

      Endocr J. 53

      Pages: 325-330

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Negative correlation between bone mineral density and TSH receptor antibodies in male patients with untreated Graves' disease.2006

    • Author(s)
      Majima T, Komatsu Y, Doi K, Takagi C, Shigemoto M, Fukao A, Morimoto T, Corners J, Nakao K.
    • Journal Title

      Osteoporos Int. 17

      Pages: 1103-1110

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of the aderenomedullin gene in adipose tissue.2005

    • Author(s)
      Nambu T, Arai H, Komatsu Y, Yasoda A, Moriyama K, Kanamoto N, Itoh H, Nakao K
    • Journal Title

      Regul Pept 132

      Pages: 17-22

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Anaplastic thyroid carcinoma associated with Graves' disease2005

    • Author(s)
      Majima T, Komatsu Y, Doi K, Shigemoto M, Takagi C, Fukao A, Kojima M, Tamaki H, Ito J, Nakao K
    • Journal Title

      Endocrinol J 52

      Pages: 551-557

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Papillary thyroid carcinoma without metastases manifesting as an autonomously functioning thyroid nodule2005

    • Author(s)
      Majima T, Doi K, Komatsu Y, Itoh H, Fukao A, Shigemoto M, Takagi C, Corners J, Mizuta N, Kato R, Nakao K
    • Journal Title

      Endocrin J 52

      Pages: 309-316

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Complementary antagonistic actions between C-Type natriuretic peptide and MAPK pathway through FGFR-3 in ATDC5 Cells.2005

    • Author(s)
      Ozasa A, Komatsu Y, Yasoda A, Miura M, Nakatsuru Y, Sakuma Y, Arai H, Itoh N, Nakao N
    • Journal Title

      Bone 36

      Pages: 1056-1064

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Primary hyperparathyroidism presumably caused by chronic parathyroiditis manifesting from hypocalcemia to severe hypercalcemia.2005

    • Author(s)
      Furuto-Kato S, Matsukura S, Ogata M, Azuma N, Manabe T, Shigeno C, Asato R, Tanaka K, Komatsu Y, Nakao K
    • Journal Title

      Intern Med 44

      Pages: 60-64

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Decreased bone mineral density at the distal radius, but not at the lumbar spine or the femoral neck, in Japanese type 2 diabetic patients.2005

    • Author(s)
      Majima T, Komatsu Y, Yamada T, Koike Y, Shigemoto M, Takagi C, Hatanaka I, Nakao K
    • Journal Title

      Osteoporos Int 16

      Pages: 907-913

    • Description
      「研究成果報告書概要(和文)」より

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Published: 2008-05-27  

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