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Molecular and cellular approaches to the treatment of degenerative lumbar disc disease

Research Project

Project/Area Number 17591595
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

CHIBA Kazuhiro  Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (80179952)

Co-Investigator(Kenkyū-buntansha) TAKAISHI Hironari  Keio University, School of Medicine, Research Associate, 医学部, 助手 (60236180)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordscell and tissue / intervertebral disc / bioactive molecules / degeneration / low back pain / CD24 / 再生医療 / マイクロアレイ / 脊索 / 髄核細胞 / 加齢変性 / 表面マーカー
Research Abstract

There are several avascular tissues such as intervertebral disc, cartilage and lens. However, how these tissues are maintained without blood flow is poorly understood. Among the avascular tissues, we focused on nucleus pulposus (NP), avascular component of intervertebral disc. To explore what molecules are expressed in NP, microarray analysis was performed in NP and other eleven different tissues. Interestingly, we found that Vascular Endothelial Growth Factor (VEGF) was highly expressed in NP when compared with other tissues
To analyse role of VEGF in NP, VEGF expression in NP was confirmed by western blotting and RT-PCR analysis. All splice variants of VEGF were detected in NP. -Expressions of hypoxic response genes such as GLUT-1 and PGK-1 as well as VEGF were higher in NP cells than other tissues, and NP was hypoxic marker, pimonidazole, positive tissues. Moreover, VEGF expression in NP cells was up-regulated under hypoxic conditions and not in normoxic conditions in vitro suggestin … More g that VEGF expression in NP is promoted by hypoxia. Among VEGF receptors, the expression of Flt-1 but not Flk-1 was detected in NP by RT-PCR analysis, and this finding was confirmed by LacZ staining of NP in Flt-1-lacZ and Flk-1-lacZ knock-in mice. These results suggest that VEGF may function as an anti-apoptotic factor in NP cells through Flt-1 as autocrine or paracrine loop. In in vitro, numbers of apoptotic cells was increased by addition of Flt-1-Fc but not by CD4-Fc. Thus, anti-apoptosis may be one of functions of VEGF in NP cells. In MRI analysis, T2 high signal intensity of intervertebral disc, which indicate a healthy NP, decreased with aging in rat as seen in human. As T2 high signal decreased with aging, the VEGF mRNA expression in NP was down-regulated, which also correlated with down-regulation of expression of chondrogenic markers such as aggrecan and type II collagen.
Taken together, our results demonstrate that VEGF-Flt-1 signal may play role in NP survival in autocrine/paracrine manner. Now, we have started analysis on function of VEGF in NP cells using Flt-1-TK/TK mice, which has Flt-1 signaling deficiency because of disruption of cytoplasmic domain of Flt-1. Less

Report

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

    (12 results)

All 2006 2005

All Journal Article (12 results)

  • [Journal Article] Association study of COL9A2 with lumbar disc disease in the Japanese population.2006

    • Author(s)
      Seki S, et al.
    • Journal Title

      J Hum Genet 51 (12)

      Pages: 1063-1067

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel hydroxyapatite fiber mesh as a carrier for recombinant human bone morphogenetic protein-2 enhances bone union in rat posterolateral fusion model.2006

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

      Spine 31 (11)

      Pages: 1194-1200

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ischemia-induced disturbance of neuronal network function in rat spinal cord analyzed by voltage-imaging.2006

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

      Neuroscience 140 (4)

      Pages: 1453-1465

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.2006

    • Author(s)
      Horikoshi T, et al.
    • Journal Title

      Hum Genet 119 (6)

      Pages: 611-666

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association study of COL9A2 with lumbar disc disease in the Japanese population.2006

    • Author(s)
      Seki S, Kawaguchi Y, Mori M, Mio F, Chiba K, Mikami Y, Tsunoda T, Kubo T, Toyama Y, Kimura T, Ikegawa S.
    • Journal Title

      J Hum Genet. 51(12)

      Pages: 1063-7

    • NAID

      10018641536

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A novel hydroxyapatite fiber mesh as a carrier for recombinant human bone morphogenetic protein-2 enhances bone union in rat posterolateral fusion model.2006

    • Author(s)
      Morisue H, Matsumoto M, Chiba K, Matsumoto H, Toyama Y, Aizawa M, Kanzawa N, Fujimi TJ, Uchida H
    • Journal Title

      Spine. 31(11)

      Pages: 1194-200

    • NAID

      10020594510

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Ischemia-induced disturbance of neuronal network function in the rat spinal cord analyzed by voltage-imaging.2006

    • Author(s)
      Fukuda K, Okada Y, Yoshida H, Aoyama R, Nakamura M, Chiba K, Toyama Y.
    • Journal Title

      Neuroscience 140(4)

      Pages: 1453-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.2006

    • Author(s)
      Horikoshi T, Maeda K, Kawaguchi Y, Chiba K, Mori K, Matsumoto M, Kawaguchi H, Nakamura K, Ikegawa S.
    • Journal Title

      Hum Genet 119(6)

      Pages: 611-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Association study of COL9A2 with jumbar disc disease in the Japanese population.2006

    • Author(s)
      Seki S, Kawaguchi Y, Mori M, Mio F, Chiba K, Mikami Y, Tsunoda T, Kubo T, Toyama Y, Kimura T, Ikegawa S.
    • Journal Title

      J Hum Genet 51(12)

      Pages: 1063-7

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel hydroxyapatite fiber mesh as a carrier for recombinant human bone morphogenetic protein-2 enhances bone union in rat posterolateral fusion model.2006

    • Author(s)
      Morisue H, Matsumoto M, Chiba K, Matsmoto H, Toyama Y, Aizawa M, Kanzawa N, Fujimi TJ, Uchida H
    • Journal Title

      Spine 31(11)

      Pages: 1194-200

    • NAID

      10020594510

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Ischemia-induced disturbance of neuronal network fnction in the rat spinal cord analyzed by voltage-imaging.2006

    • Author(s)
      Fukuda K, Okada Y, Yoshida H, Aoyama R, Nakamura M, Chiba K, Toyama Y.
    • Journal Title

      Neuroscience 140(4)

      Pages: 1453-65

    • Related Report
      2006 Annual Research Report
  • [Journal Article] CD24 is expressed specifically in the nucleus pulposus of intervertebral discs2005

    • Author(s)
      Fujita N, Chiba K.et al.
    • Journal Title

      Biochem Biophys Res Commun. 338(4)

      Pages: 1890-1896

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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