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Functional analysis of plasminogen related genes in cartilage metabolism

Research Project

Project/Area Number 18591677
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKeio University

Principal Investigator

MORIOKA Hideo  Keio University, School of Medicine, Assistant professor (10230096)

Co-Investigator(Kenkyū-buntansha) TOYAMA Yoshiaki  Keio University, School of Medicine, Professor (40129549)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,490,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsJoint disease / Rheumatoid arthritis / Osteoarthritis / Bone and Cartilage metabolism / Angiogenesis / Cartilage / Synovium / Synovitis
Research Abstract

The purpose of this study is to clarify the role of PRGB and PRPB in arthritis joint such as RA. We investigated the expression of PRGB and the role of PRPB in the main components, synovium and cartilage, in rheumatoid arthritis closely involving angiogenesis. PRGB was not expressed in synoviocytes under normal conditions in vitro, and expression was not induced, even when the cells were stimulated with cytokines (IL-1 and bFGF) to mimic a condition similar to rheumatoid arthritis. In cartilage, PRGB was not expressed in chondrocytes under normal conditions, but the expression was enhanced by cytokine stimulation. On ISH, PRGB was not expressed in the synovial membrane, but was partially expressed in joint cartilage with RA. These findings suggested that PRGB is not expressed in normal joint cartilage, but that the expression is enhanced when stimulated, such as during inflammation, although the mechanism remains unclear. To investigate the action of PRGB, we prepared the recombinant P … More RGB protein (PRPB). In RA, the influence of PRPB on synoviocytes was investigated because synovium growth is involved in the pathogenesis. Synoviocytes proliferated when stimulated with cytokines (IL-1 and bFGF). However, PRPB did not inhibit the proliferation. Thus, we focused on the hypothesis that VEGF could strongly induce new blood vessel formation in inflammatory synovium in RA, and investigated the influence of PRPB on VEGF expression. Firstly, we added PRPB to synoviocytes and chondrocytes stimulated with cytokines (IL-1 and bFGF), and investigated the changes in VEGF expression at the gene and protein levels. PRPB significantly inhibited VEGF expression in synoviocytes at both the gene and protein levels, and in cartilage at the gene level. For in vivo study, CIA mice that are presumed to represent the pathology of rheumatoid arthritis were used. The paw thickness was significantly reduced over the time in the PRPB treatment group, compared to that in the control group treated with PBS. In addition, bone erosion and destruction were reduced on micro CT. Histopathologically, synovium growth and bone destruction were both reduced, and the number of CD31-positive vascular endothelial cells was also decreased on immunostaining of vascular endothelial cells in the articular synovial tissue with anti-CD31 antibody. It was suggested that arthritis was inhibited and angiogenesis was suppressed in the PRPB treatment group. Regarding the action of PRPB on vascular endothelial cells, the inhibitory effect was exerted via integrin. It was also suggested that inhibition of VEGF produced by the synovial tissue suppressed angiogenesis. The mechanism of action of the inhibition of VEGF by PRPB remains to be investigated. This study confirmed that PRPB inhibits arthritis by suppressing angiogenesis, but many of the details of the mechanism of action are unclear and remain to be investigated. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (3 results)

All 2007

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

  • [Journal Article] Hyaline cartilage formation and enchondral ossification modeled with KTM5 and OP9 chondroblasts.2007

    • Author(s)
      Sugiki T, Morioka H, et. al.
    • Journal Title

      J Cell Biochem 100

      Pages: 1240-1254

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Localized pigmented villollodular synovitis presenting as a loose body following minor trauma in the knee:A case report2007

    • Author(s)
      Kanagawa H, Morioka H, et. al.
    • Journal Title

      Knee 14

      Pages: 395-397

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 分子レベルからみた整形外科疾患血管新生の制御による骨軟部腫瘍の治療2007

    • Author(s)
      森井 健司、森岡 秀夫
    • Journal Title

      整形・災害外科 50

      Pages: 1380-1381

    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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