• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2005 Fiscal Year Final Research Report Summary

Analysis of genes related to the ectopic bone formation induced by mechanical stress and search for drugs targeting the genes.

Research Project

Project/Area Number 16390063
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionHirosaki University

Principal Investigator

FURUKAWA Ken-Ichi  Hirosaki University School of Medicine, Department of Pharmacology, Associate Professor, 医学部, 助教授 (20165468)

Co-Investigator(Kenkyū-buntansha) INOUE Ituro  The University of Tokyo, Division of genetic diagnosis, The Institute of Medical Science, Associate Professor, 医科学研究所, 客員助教授 (00192500)
OKADA Akihiro  Hirosaki University Hospital, Orthopedic Surgery, Lecturer, 医学部附属病院, 講師 (90312488)
SEYA Kazuhiko  Hirosaki University School of Medicine, Department of Pharmacology, Assistant, 医学部, 助手 (40281919)
Project Period (FY) 2004 – 2005
Keywordsectopic bone formation / mechanical stress / microarray / gene expression / siRNA / Cbfa1 / nucleotide receptor / endochondral ossification
Research Abstract

To clarify the cause of the ossification of posterior longitudinal ligament (OPLL), comprehensive analyses by cDNA microarray method were carried out using cultured human spinal ligament cells that had been subjected to uniaxial cyclic stretching (mechanical stress). Microarray analyses showed the up-regulation of many ossification-marker genes including alkaline phosphatase, osteocalcin, collagen type I and Cbfa1, by cyclic stretching in ligament cells from OPLL patients but not in normal ligament cells, suggesting that OPLL cells are higher sensitive to mechanical stress than normal ligament cells. The higher sensitivity to mechanical stress was also confirmed in ligament tissue from OPLL patients. These results suggest that mechanical stress participates in the progression of OPLL through changes in expressions of various genes related to bone metabolism.
Spectrum of P2 receptor subtype expression in OPLL cells was quite different from that in non-OPLL cells. Especially, P2Y1 expression in OPLL cells was much higher than that in non-OPLL cells and almost equal to that in SaOS2 (osteosarcoma cell line). ATP as a P2Y1 agonist increased the expressions of osteogenic markers such as ALP and osteopontin in OPLL cells but not in non-OPLL cells. These increases were almost diminished in the presence of P2Y1-specific antagonist. Furthermore, mechanical stress increased ATP release from OPLL cells remarkably. These results suggest that as one of extracellular factors influencing the process of ossification, a pathophysiological action of ATP via P2Y1 is important. They become a novel pharmacotherapeutic target for OPLL.

  • Research Products

    (11 results)

All 2006 2005 2004

All Journal Article (11 results)

  • [Journal Article] Current topics in pharmacological research on bone metabolism2006

    • Author(s)
      Ken-Ichi Furukawa
    • Journal Title

      Journal of Pharmacological Science 100

      Pages: 187

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular basis of ectopic bone formation induced by mechanical stress.2006

    • Author(s)
      Ken-Ichi Furukawa
    • Journal Title

      Journal of Pharmacological Science 100

      Pages: 201-204

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] PLZF and TSG-6 identified by gene expression analysis play roles in the pathogenesis of OPLL2006

    • Author(s)
      Ituro Inoue
    • Journal Title

      Journal of Pharmacological Science 100

      Pages: 205-210

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 難病と在宅ケア2006

    • Author(s)
      古川賢一
    • Journal Title

      脊柱靱帯骨化症の薬物治療法開発を目指して 12

      Pages: 11-14

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Current topics in pharmacological research on bone metabolism2006

    • Author(s)
      Ken-Ichi Furukawa, et al.
    • Journal Title

      Journal of Pharmacological Science 100

      Pages: 187

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] PLZF and TSG-6 identified by gene expression analysis play roles in the pathogenesis of OPLL2006

    • Author(s)
      Ituro Inoue, et al.
    • Journal Title

      Journal of Pharmacological Science 100

      Pages: 205-210

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Aiming at the development of pharmacotherapy for OPLL2006

    • Author(s)
      Ken-Ichi Furukawa
    • Journal Title

      Nanbyo to Zaitakukea 12

      Pages: 11-14

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] PLZF promotes osteoblastic differentiation of human mesenchymal stem cells as an upstream regulator of CBFA1.2005

    • Author(s)
      Ryuji Ikeda
    • Journal Title

      Journal of Biological Chemistry 280

      Pages: 8523-8530

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] PLZF promotes osteoblastic differentiation of human mesenchymal stem cells as an upstream regulator of CBFA1.2005

    • Author(s)
      Ryuji Ikeda et al.
    • Journal Title

      Journal of Biological Chemistry 280

      Pages: 8523-8530

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Uni-axial cyclic stretch induces Cbfal expression in spinal ligament cells derived from patients with ossification of posterior longitudinal ligaments.2004

    • Author(s)
      Koei Iwasaki
    • Journal Title

      Calcified Tissue International 74

      Pages: 448-457

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Uni-axial cyclic stretch induces Cbfa1 expression in spinal ligament cells derived from patients with ossification of posterior longitudinal ligaments.2004

    • Author(s)
      Koei Iwasaki et al.
    • Journal Title

      Calcified Tissue International 74

      Pages: 448-457

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

URL: 

Published: 2007-12-13  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi