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Cell-specific response to mechanical stress and regulatory mechanism of differentiation : ligament/tendon cells versus osteoblasts

Research Project

Project/Area Number 16390531
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionNiigata University

Principal Investigator

KAWASHIMA Hiroyuki  Niigata University, Institute of Medicine and Dentistry, Department of Tissue Regeneration and Reconstruction, Professor, 医歯学系, 教授 (40169719)

Co-Investigator(Kenkyū-buntansha) YOSHIZAWA Tatsuya  Niigata University, Institute of Medicine and Dentistry, Department of Tissue Regeneration and Reconstruction, Assistant, 医歯学系, 助手 (40313530)
ISHIBASHI Osamu  Niigata University, Institute of Medicine and Dentistry, Department of Tissue Regeneration and Reconstruction, Assistant, 医歯学系, 助手 (70293214)
松田 明生  新潟大学, 大学院・医歯学総合研究科, 助手 (10359705)
里方 一郎  新潟大学, 大学院・医歯学総合研究科, 教授 (70170800)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2006: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥8,200,000 (Direct Cost: ¥8,200,000)
Keywordsmechanical stress / ligament cells / osteoblasts / mechanism of mineralization / integrins / Msx2 / PIASxβ / osterix / PIASXβ / 遺伝子発現 / OPLL
Research Abstract

Using PDL-L2, a ligament cell line established in our laboratory, we have demonstrated the followings:
(1) Ligament cells have characteristics of osteoblastic cells at the early stage of osteoblast differentiation.
(2) Ligament cells do not produce mineralized nodule in vitro in spite of expressing Runx2, a key transcription factor for osteoblast differentiation
(3) This is due to suppression of Runx2 activity by homeobox protein Msx2.
(4) Overexpression of Msx2 suppresses matrix mineralization by osteoblasts
(5) Conversely, knockdown of Msx2 causes matrix mineralization by ligament cells
(6) Mechanical stress accelerates and enhances matrix mineralization by osteoblasts, but without effect on ligament cells.
(7) This is likely due to difference in integrins between these two cell types.
Furthermore, we identified PIASxβ, first identified as an E3 ligase, as a key regulator for mineralization. The observations includes
(8) For matrix mineralization, a transient increase of PIASxβ is required at an early stage of osteoblast differentiation and this is also required for mechanical stress-induced mineralization.
(9) This effect of PIASxβ is sumoylation-dependent and through activation of osterix, another key transcription factor for osteoblast differentiation located at the immediate downstream of Runx2. Thus PIASxβ is a signaling molecule between Runx2 and osterix in osteoblast differentiation and mineralization.
(10) Osterix promoter is auto-regulated by itself and this may play an important role in controlling matrix mineralization by osteoblasts.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (6 results)

All 2005 2004 Other

All Journal Article (6 results)

  • [Journal Article] Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated ras mutation2005

    • Author(s)
      川島 寛之 他7名
    • Journal Title

      J.Exp.Clin.Cancer Res. 24・4

      Pages: 617-624

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Integrin α7 prevents mechnical stress-induced mineralization of ligaments2005

    • Author(s)
      滝沢 史夫 他8名
    • Journal Title

      J.Bone Miner.Res. 20・suppl.1

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Homeobox protein Msx2 acts as a molecular-defense mechanism for preventing ossification in ligament fibroblasts2004

    • Author(s)
      吉澤 達也 他7名
    • Journal Title

      Mol.Cell.Biol. 24・8

      Pages: 3460-3472

    • Related Report
      2004 Annual Research Report
  • [Journal Article] PIASxβ is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts

    • Author(s)
      MD Moksed Ali 他
    • Journal Title

      J. Cell Sci. (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] PIASxp is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts

    • Author(s)
      MD Moksed Ali, et al.
    • Journal Title

      J.Cell Sci. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] PIASxβ is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts

    • Author(s)
      MD Moksed Ali 他
    • Journal Title

      J. Cell Sci. (印刷中)

    • Related Report
      2006 Annual Research Report

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

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