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Basic studies of a gene therapy approach for osteoblastic (odontoblastic) disability in inherited and tumor-induced hypophosphatemic disorders

Research Project

Project/Area Number 16591828
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

YOSHIKO Yuji  Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20263709)

Co-Investigator(Kenkyū-buntansha) WANG Hua  Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (50363081)
KODAMA Ichiro  Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (00325169)
田中 雅治  小野薬品工業(株), 福井安全性研究所, 課長
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsosteobast / inorganic phosphate / Pit1 / stanniocalcin 1 / ricket / osteomalacia / chondrocyte / 軟骨 / スタニオカルシン / リン酸 / 骨軟化症・くる病 / NaPiトランスポーター / アデノウイルス / 骨形成 / 培養
Research Abstract

Inorganic phosphate (Pi) is indispensable for skeletal development not only for its role in hydroxyapatite crystal formation but also as a signaling molecule for multiple cellular events during chondogenesis and osteoclastic bone resorption. Additionally, the complex pathogenesis of mineralization defects seen in inherited and/or acquired hypophosphatemic disorders suggests that local Pi regulation may contribute to osteoblast-mediated bone mineralization. In these backgrounds, we established following results :
1.Foscarnet, an inhibitor of sodium-dependent Pi (NaPi) cotransport blocked mineralization in vivo and vitro without systemic side effects or effects on osteoid formation.
2.Mineralization was also inhibited or stimulated respectively with under- and overexpression of the type III sodium-dependent Pi (NaPi) cotransporter Pit1 in vitro.
3.Stanniocalcin 1 (STC1), a known calcium/phosphate regulating molecule, increased Pit1 accumulation and NaPi uptake, resulting in acceleration of mineralization in vivo and vitro.
4.STC1 increased chondrocyte apoptosis concomitant with the increased Pi uptake and the decreased fibroblast growth factor 23 expression.
5.The effects of STC1 on chondocytes were reversed by foscarnet.
These results provide new insights into the functional role of local Pi-handling by osteoblasts and chondrocytes in normal skeletal development and the abnormalities seen in skeletal tissue in hypophosphatemic disorders.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (3 results)

All 2006

All Journal Article (3 results)

  • [Journal Article] Stanniocalcin I acts as a paracrine regulator of growth plate chondrogenesis.2006

    • Author(s)
      Wu, S
    • Journal Title

      J Biol Chem 281

      Pages: 5120-5127

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Stanniocalcin 1 acts as aparacrine regulator of growth plate chondrogenesis.2006

    • Author(s)
      Wu S
    • Journal Title

      J Biol Chem 281(8)

      Pages: 5120-5127

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Stanniocalcin 1 acts as a paracrine regulator of growth plate chondrogenesis.2006

    • Author(s)
      Wu, S
    • Journal Title

      J Biol Chem 281

      Pages: 5120-5127

    • Related Report
      2005 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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