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骨芽細胞の増殖、分化、老化におけるホルモン応答性に関わる細胞周期制御因子の同定

Research Project

Project/Area Number 15689014
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Endocrinology
Research InstitutionThe University of Tokyo

Principal Investigator

浦野 友彦  東京大学, 医学部附属病院, 助手 (20334386)

Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥29,510,000 (Direct Cost: ¥22,700,000、Indirect Cost: ¥6,810,000)
Fiscal Year 2005: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2004: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2003: ¥15,340,000 (Direct Cost: ¥11,800,000、Indirect Cost: ¥3,540,000)
Keywords骨粗鬆症 / 骨形成 / 骨芽細胞 / 遺伝子多型 / 遺伝子マーカー / LRP5 / Wntシグナル / 老化
Research Abstract

骨粗鬆症に対する治療において、骨芽細胞による骨形成を亢進させて骨量増加作用を起こすことが理想ではあるが、現在まで強力な骨形成促進役は存在していない。骨形成促進薬開発のためには、内分泌ホルモンをはじめとした液性因子による骨芽細胞の増殖と分化の制御機構を解明し、骨形成シグナルにおける中心的な役割を果たす骨芽細胞内でのシグナル伝達因子を同定することが重要と考え、以下の検討を行った。
近年、脊椎動物のシグナル伝達においてWntシグナル伝達経路が注目され、特に骨形成においてはWntに対する受容体として機能するLRP5が注目されている。本研究では、LRP5遺伝子上における29種類の遺伝子多型を解析し、LRP5遺伝子のアミノ酸変異を伴う遺伝子多型(A1330V)が閉経後女性の骨密度に影響を与えることを発見した(Bone, in press)。申請者は同時にLRP5遺伝子上の別のアミノ酸変異を伴う遺伝子多型(Q89R)が変形性腰椎症と関連することを見出しており、Wntシグナルが骨や軟骨の老化に関与する可能性が示唆された(Spine, in press)。
一方、核内受容体の一つであるSXRは骨粗鬆症治療薬であるビタミンKに対する受容体として働き、骨芽細胞機能を調整することが近年明らかにされた。しかしながら正常ヒト骨組織でのSXRの発現や骨疾患との関連は未だ明らかにされていない。本研究において、ヒトSXR遺伝子が初代培養ヒト骨芽細胞ならびに軟骨細胞において発現すること、ならびにヒトSXR遺伝子における遺伝子多型が閉経後女性の骨密度に影響を及ぼすことを発見した(Geriatri Gerontol Int, in press)。

Report

(3 results)
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (14 results)

All 2005 2004 Other

All Journal Article (10 results) Publications (4 results)

  • [Journal Article] Association of a single nucleotide polymorphism in the lipoxygenase ALOX15 5'-flanking region (-5229G/A) with bone mineral density.2005

    • Author(s)
      Urano T, Shiraki M, Inoue S
    • Journal Title

      J Bone Miner Metab 23

      Pages: 226-230

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carcinoma.2005

    • Author(s)
      Ogushi T, Takahashi S, Inoue S et al.
    • Journal Title

      Cancer Res 65

      Pages: 3700-3706

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Estrogen-responsive finger protein as a new potential biomarker for breast cancer.2005

    • Author(s)
      Suzuki T, Urano T, Inoue S
    • Journal Title

      Clin Cancer Res 11

      Pages: 6148-6154

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of a single nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density.2004

    • Author(s)
      Urano T, Ouchi Y, Inoue S et al.
    • Journal Title

      J Bone Miner Metab 22

      Pages: 341-345

    • NAID

      10013606144

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association of a single nucleotide polymorphism in the secreted frizzled related protein 4 (sFRP4) gene with bone mineral density.2004

    • Author(s)
      Fujita M, Urano T, Inoue S et al.
    • Journal Title

      Geriatric Gerontol Int 4

      Pages: 175-180

    • NAID

      10014317168

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 14-3-3sigma is down-regulated in human prostate cancer.2004

    • Author(s)
      Trano T, Takahashi S, Inoue S et al.
    • Journal Title

      Biochem Biophys Res Commun 319

      Pages: 795-800

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women.

    • Author(s)
      Ezura Y, Inoue S, Emi M et al.
    • Journal Title

      Bone (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of a single nucleotide polymorphism in the steroid and xenobitic receptor (SXR) gene (IVS1-579A/G) with bone mineral density.

    • Author(s)
      Urano T, Shiraki M, Inoue S et al.
    • Journal Title

      Geriatric Gerontol Int (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Q89R polymorphism in the LDL receptor-related protein 5 gene is associated with spinal osteoarthritis in postmenopausal Japanese women.

    • Author(s)
      Urano T, Shiraki M, Inoue S et al.
    • Journal Title

      Spine (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Association of a single nucleotide polymorphism in the lipoxygenase ALOX15 5'-flanking region (-5229G/A) with bone mineral density.

    • Author(s)
      Urano T, Shiraki M, Inoue S et al.
    • Journal Title

      J Bone Miner Metab (in press)

    • Related Report
      2004 Annual Research Report
  • [Publications] Urano T, Ouchi Y, Inoue S, et al.: "Association of a single nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density."J.Bone Miner.Metab.. (in press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Takahashi S, Urano T, Inoue S, et al.: "EBAG9/RCAS1 expression and its prognostic significance in prostatic cancer."Int.J.Cancer. 106. 310-315 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Aoki T, Inoue S, Makuuchi M, et al.: "EBAG9/RCAS1 expression in hepatocellular carcinoma : correlation with tumour dedifferentiation and proliferation."Eur.J.Cancer. 39. 1552-1561 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Horie K, Urano T, Inoue S, et al.: "Estrogen-responsive RING finger protein controls breast cancer growth."J.Steroid Biochem.Mol.Biol.. 85. 101-104 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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