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2007 Fiscal Year Final Research Report Summary

Therapeutic research for osteoporosis with rheumatoid arthritis

Research Project

Project/Area Number 18591129
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionUniversity of Occupational and Environmental Health, Japan

Principal Investigator

OKADA Yosuke  University of Occupational and Environmental Health, Japan, School of Medicine, Assistant Professor (80333243)

Co-Investigator(Kenkyū-buntansha) TANAKA Yoshiya  University of Occupational&Environmental Health, School of Medicine, Professor (30248562)
Project Period (FY) 2006 – 2007
KeywordsRA synovial endothelial cells / M-CSF / RANKL / Osteoblast / Osteoclast
Research Abstract

Objective. Periarticular osteoporosis and joint destruction are major complications in rheumatoid arthritis (RA), caused by osteoclast-mediated bone resorption. However, the mechanisms of monocyte/osteoclast maturation and 'role of RA endothelial cells (RAECs) in the control of osteoclastogenesis remain unclear. The present study was designed to determine the most important factors that influence monocyte accumulation and osteoclast formation among the many factors produced by RAEC.
Methods. We analyzed the expression profiles of various genes in human endothelial cells from various organs (RA synovium, umbilical vein, skin, liver sinusoid, renal glomerulus and brain) using oligonucleotide microarrays. Specifically, up-regulated gene in RAECs was assessed by real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and immunostaining of RA synovia. Migration of monocytes was assessed by the chemotactic chamber EZ-TAXIScanTM. Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell formation was observed by microscopy.
Results. Among many epithelial-expressed factors, macrophage-colony stimulating factor (M-CSF) gene was abundantly expressed specifically in RAECs. Genes of fibroblast growth factor-2, interleukin-6 and osteoprotegerin were also overexpressed on RAECs. Migration of monocytes and osteoclast formation in co-cultures promoted by culture supernatants of RAEC were inhibited by M-CSF neutralizing antibody.
Conclusion. M-CSF produced by RAECs is involved in osteoclastogenesis from monocytes, migration and TRAP-positive MNC formation.

  • Research Products

    (8 results)

All 2007

All Journal Article (6 results) (of which Peer Reviewed: 3 results) Presentation (2 results)

  • [Journal Article] Rheumatoid synovial endothelial cells produce macrophage-colony stimulating factor leading to osteoclastogenesis of rheumatoid arthritis2007

    • Author(s)
      Nakano K, et. al.
    • Journal Title

      Rheumatology 46

      Pages: 597-603

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] GTPase Rho signaling is involved in beta 1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor kappa B ligand on osteoblasts and osteoclast maturation2007

    • Author(s)
      Hirai F, et. al.
    • Journal Title

      Biochem Biophys Res Commun 356

      Pages: 279-285

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Cyclooxygenase-2 gene disruption promotes proliferation of murine calvarial osteoblasts in vitro2007

    • Author(s)
      Xu A, et. al.
    • Journal Title

      Bone 41

      Pages: 68-76

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Rheumatoid synovial endothelial cells produce macrophage-colony stimulating factor leading to osteoclastogenesis of rheumatoid arthritis.2007

    • Author(s)
      Nakano Y, et. al.
    • Journal Title

      Rheumatology 46

      Pages: 597-603

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] GTPase Rho signaling is involved in beta 1 integrin-rnediatedupregulation of intercellular adhesion molecule 1 and receptor activator ofupregulation of intercellular adhesion molecule 1 and receptor activator of2007

    • Author(s)
      Hirai F, et. al.
    • Journal Title

      Biochem Biophys Res Commun 356

      Pages: 279-285

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cyclooxygenase-2 gene disruption promotes proliferation of murinecalvarial osteoblasts in vitro.2007

    • Author(s)
      Xu A, et. al.
    • Journal Title

      Bone 41

      Pages: 68-76

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Treatment with anti-TNF-a antibody recovers osteoclast maturation deriated from bone remodeling cycle in RAjoint destruction2007

    • Author(s)
      Nawata M, et. al.
    • Organizer
      American Society of Bone and minereal Research
    • Place of Presentation
      Hawali
    • Year and Date
      20070900
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Treatment with anti-TNF-α antibody recovers osteoclast maturation deriated from bone remodeling cycle in RA joint destruction2007

    • Author(s)
      Nawata M, et. al.
    • Organizer
      American Society for Bone and Mineral Research Meeting
    • Place of Presentation
      Hawaii
    • Year and Date
      2007-09-19
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-02-04  

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