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Physiological and pathological involvement of FGF-23 in mineral metabolism in human

Research Project

Project/Area Number 17590972
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionOkinaka Memorial Institute for Medical Research

Principal Investigator

TAKEUCHI Yasuhiro  Okinaka Memorial Institute for Medical Research, Investigator, 研究員 (50202164)

Co-Investigator(Kenkyū-buntansha) TAKESHITA Akira  Okinaka Memorial Institute for Medical Research, Investigator, 研究員 (20322646)
TAGUCHI Manabu  Okinaka Memorial Institute for Medical Research, Investigator, 研究員 (00265141)
FUKUMOTO Seiji  University of Tokyo School of Medicine, Department of Nephrology and Endocrinology, Lecturer, 医学部附属病院, 講師 (30202287)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsFGF-23 / phosphate metabolism / vitamin D metabolism / tumoral calcinosis / acromegaly
Research Abstract

1) Mutation of FGF-23 gene involved in tumoral calcinosis
We identified mutation of FGF-23 gene in patients with familial tumoral calcinosis. Missense mutation was found. Expression the mutated FGF-23 gene in mammalian cells resulted in remarkable degradation of FGF-23 protein with essentially no full-length and active FGF-23 in culture media. Serum level of full-length FGF-23 was almost undetectable in patients with tumoral calcinossis we evaluated, although degradation products of FGF-23 were accumulated in circulating blood. These data indicate that loss of function of FGF-23 in human causes tumoral calcinosis that presents hyperphosphatemia and high serum level of 1,25-dihydroxyvitamin D.
2) Response of circulating FGF-23 to acute increase in serum phosphate level in healthy volunteers
When serum phosphate level was increased with intravenous infusion of dibasic potassium phosphate to 6.0 mg/dl, circulating level of FGF-23 did not change significantly within 6 hours of experiments. This result suggests that in contrast to rapid decrease in PTH secretion in response to hypercalcemia, secretion of FGF-23 cannot respond to acute changes of serum phosphate level. Physiological mechanisms for regulation of serum FGF-23 level are to be explored with further studies.
3) Serum phosphate and FGF-23 levels in patients with acromegaly before and after pituitary surgery
Serum phosphate level is higher in patients with acromegaly and decreases normally after successful surgery. When clinical laboratory data of consecutive 17 patients with acromegaly were analyzed, serum level of FGF-23 also concomitantly decreased with pituitary surgery. This indicates secretion of FGF-23 promptly responds to the decrease in serum phosphate level in human.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (17 results)

All 2006 2005 Other

All Journal Article (17 results)

  • [Journal Article] Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.2006

    • Author(s)
      Shinoda Y et al.
    • Journal Title

      J Cell Biochem 99 (1)

      Pages: 196-208

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.2006

    • Author(s)
      Shinoda Y, Yamaguchi M, Ogata N, Akune T, Kubota N, Yamauchi T, Terauchi Y, Kadowaki T, Takeuchi Y, Fukumoto S, Ikeda T, Hoshi K, Chung UI, Nakamura K, Kawaguchi H
    • Journal Title

      J Cell Biochem 99 (1)

      Pages: 196-208

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.2006

    • Author(s)
      Shinoda Y et al.
    • Journal Title

      J Cell Biochem 99(1)

      Pages: 196-208

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis.2005

    • Author(s)
      Araya K et al.
    • Journal Title

      J Clin Endocrinol Metab 90 (10)

      Pages: 5523-5527

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparison of two assays for fibroblast growth factor (FGF)-23.2005

    • Author(s)
      Ito N et al.
    • Journal Title

      J Bone Miner Metab 23 (6)

      Pages: 435-440

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ghrelin directly regulates bone formation.2005

    • Author(s)
      Fukushima N et al.
    • Journal Title

      J Bone Miner Res 20 (5)

      Pages: 790-798

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 1,25-Dihydroxyvitamin D suppresses circulating levels of parathyroid hormone in a patient with primary hyperparathyroidism and coexistent sarcoidosis.2005

    • Author(s)
      Kinoshita Y et al.
    • Journal Title

      J Clin Endocrinol Metab 90 (12)

      Pages: 6727-6731

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis.2005

    • Author(s)
      Araya K, Fukumoto S, Backenroth R, Takeuchi Y, Nakayama K, Ito N, Yoshii N, Yamazaki Y, Yamashita T, Silver J, Igarashi T, Fujita T.
    • Journal Title

      J Clin Endocrinol Metab 90 (10)

      Pages: 5523-5527

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ghrelin directly regulates bone formation.2005

    • Author(s)
      Fukushima N, Hanada R, Teranishi H, Fukue Y, Tachibana T, Ishikawa H, Takeda S, Takeuchi Y, Fukumoto S, Kangawa K, Nagata K, Kojima M.
    • Journal Title

      J Bone Miner Res 20 (5)

      Pages: 790-798

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 1,25-Dihydroxyvitamin D suppresses circulating levels of parathyroid hormone in a patient with primary hyperparathyroidism and coexistent sarcoidosis.2005

    • Author(s)
      Kinoshita Y, Taguchi M, Takeshita A, Miura D, Tomikawa S, Takeuchi Y
    • Journal Title

      J Clin Endocrinol Metab 90 (12)

      Pages: 6727-6731

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis.2005

    • Author(s)
      Araya K et al.
    • Journal Title

      J Clin Endocrinol Metab 90(10)

      Pages: 5523-5527

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Comparison of two assays for fibroblast growth factor(FGF)-23.2005

    • Author(s)
      Ito N et al.
    • Journal Title

      J Bone Miner Metab 23(6)

      Pages: 435-440

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Ghrelin directly regulates bone formation.2005

    • Author(s)
      Fukushima N et al.
    • Journal Title

      J Bone Miner Res 20(5)

      Pages: 790-798

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 1,25-Dihydroxyvitamin D suppresses circulating levels of parathyroid hormone in a patient with primary hyperparathyroidism and coexistent sarcoidosis.2005

    • Author(s)
      Kinoshita Y et al.
    • Journal Title

      J Clin Endocrinol Metab 90(12)

      Pages: 6727-6731

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fibroblast growth factor (FGF)23 in patients with acromegaly.

    • Author(s)
      Ito N et al.
    • Journal Title

      Endocrine J (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fibroblast growth factor (FGF) 23 in patients with acromegaly.

    • Author(s)
      Ito, N, Fukumoto S, Taguchi M, Takeshita A, Takeuchi Y, Yamada S, Fujita T.
    • Journal Title

      Endocrine J (in press)

    • NAID

      130004770047

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fibroblast growth factor (FGF)23 in patients with acromegaly.

    • Author(s)
      Ito N et al.
    • Journal Title

      Endocrine J (in press)

    • Related Report
      2006 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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