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2004 Fiscal Year Final Research Report Summary

The basic research of the mechanism and the treatment for intervertebral disc degeneration.

Research Project

Project/Area Number 15591601
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, Department of Orthopaedic Surgery, Associate Professor, 医学部, 助教授 (80179952)

Co-Investigator(Kenkyū-buntansha) TAKAISHI Hironari  Keio University, Department of Orthopaedic Surgery, Instructor, 医学部, 助手 (60236180)
Project Period (FY) 2003 – 2004
Keywordsintervertebral disc / nucleus pulposus / annulus fibrosus / degeneration / matrix / TIMP-3 / Aggrecan / collagen
Research Abstract

Objectives. Age-related changes in the expressions of TIMP-3 and TGF-β1 in the IVD were investigated to elucidate possible roles of TIMP-3 and, thereby, the notochordal NP in the maintenance of IVD homeostasis.
Summary of Background Data. Among the four TIMPs, TIMP-3 has a number of unique properties, the most interesting properties of which is to inhibit aggrecanases in addition to matrix metalloproteinases. There has been no study that identified TIMP-3 in the IVD and investigated the age-related changes in its expression to elucidate possible roles of TIMP-3 in the IVD metabolism.
Methods. Immunohistochemistry of TIMP-3 and semi-quantitative gene expression analysis of TGF-β1 and TIMP-3 were conducted using 4-week-old and 160-week-old rabbits. NP tissues were cultured in vitro in the presence of TGF-β1 and IL-1β and the levels of TIMP-3 mRNA were assessed.
Results. Immunohistochemistry revealed that TIMP-3 was positive in 4-week-old rabbits only. Semi-quantitative RT-PCR revealed that the levels of expressions of TGF-β1 and TIMP-3 mRNA were significantly higher in the immature rabbit and decreased with aging in vivo. The expression of TIMP-3 mRNA in the NP was upregulated by TGF-β1 in a dose dependent manner, but was not affected by IL-1β.
Conclusions. Decrease in the expression of TIMP-3 with aging, possibly mediated in part by the downregulation of TGF-β1, occurs in the early stage of disc degeneration. Notochordal NP may play a role in the homeostasis of IVD metabolism, by expressing TGF-β1 and TIMP-3.

  • Research Products

    (22 results)

All 2005 2004 2003

All Journal Article (22 results)

  • [Journal Article] Usefulness of neurological examination for level diagnosis in patients with cervical compressive myelopathy. Prospective comparative study with radiological examination.2005

    • Author(s)
      Matsumoto M, Ishikawa M, Ishii K, Nisizawa T, Maruiwa H, Chiba_K, Toyama Y
    • Journal Title

      J Neurosurg Spine. 2

      Pages: 535-539

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Osteogenic Protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after Chondroitinase ABC-induced in vitro chemonucleolysis2005

    • Author(s)
      Takegami K, An HS, Kumano F, Chiba K Thonar EJM-A, Singh K, Masuda K
    • Journal Title

      Spine J 5

      Pages: 231-238

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Impact of interlaminar graft materials on the fusion status in atlantoaxial transarticular screw fixation.2005

    • Author(s)
      Matsumoto M., Chiba_K., Nakamura M, Toyama Y., Ogawa J
    • Journal Title

      J Neurosurg Spine 2

      Pages: 23-26

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Morphometric analysis of the thoracic and lumbar spine in Japanese on the use of pedicle screws.2005

    • Author(s)
      Nojiri K., Matsumoto M., Chiba_K., Toyama Y.
    • Journal Title

      Surg Radiol Anat 27

      Pages: 123-128

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Morphometric analysis of the thoracic and lumbar spine in Japanese on the use of pedicle screws.2005

    • Author(s)
      Nojiri K., Matsumoto M., Chiba K., Toyama Y.
    • Journal Title

      Surg Radiol Anat 27

      Pages: 123-128

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Impact of interlaminar graft materials on the fusion status in atlantoaxial transarticular screw fixation.2005

    • Author(s)
      Matsumoto M., Chiba K., Nakamura M., Toyama Y., Ogawa J.
    • Journal Title

      J Neurosurg Spine 2

      Pages: 23-26

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Osteogenic Protein-1 is most effective in stimulating nucleus pulposus and annulus fibrosus cells to repair their matrix after Chondroitinase ABC-induced in vitro chemonucleolysis.2005

    • Author(s)
      Takegami K., An H.S., Kumano F., Chiba K., Thonar E.J.M-A., Singh K., Masuda K.
    • Journal Title

      Spine J 5

      Pages: 231-238

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Usefulness of neurological examination for level diagnosis in patients with cervical compressive myelopathy. Prospective comparative study with radiological examination.2005

    • Author(s)
      Matsumoto M, Ishikawa M, Ishii K, Nisizawa T, Maruiwa H, Chiba K, Toyama Y
    • Journal Title

      J Neurosurg Spine 2

      Pages: 535-539

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Development of a New Zealand White rabbit model of pseudoarthrosis repair and evaluation of the potential role of OP-1 to overcome pseudarthrosis.2004

    • Author(s)
      Ogawa Y., Chiba_K., Matsumoto M., Nakamura M., Takaishi H., Hirabayashi H., Hirabayashi K., Toyama Y
    • Journal Title

      J Neurosurg Spine. 2

      Pages: 168-174

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Usefulness of Neurological Examination for Level Diagnosis in Patients with Cervical Compressive Myelopathy. Prospective Comparative Study with Radiological Examination.2004

    • Author(s)
      Grauer J.N., Vaccaro A.R., Kato M., Kwon B.K., Beiner J.M., Patel T., Hilibrand A.S., Chiba K., Albert T.J
    • Journal Title

      Spine 29

      Pages: 1405-1412

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Postoperative changes of spinal curvature and range of motion in adult patients with cervical spinal cord tumors -Analysis of 51 cases and review of the literature-.2004

    • Author(s)
      Asazuma T, Nakamura M, Matsumoto M, Chiba K, Toyama Y
    • Journal Title

      J Spinal Disord Tech 17

      Pages: 178-182

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Retrospective study of surgery-related outcomes in patients with syringomyelia associated with Chiari I malformation : clinical significance of changes in the size and location of syrinx on pain relief.2004

    • Author(s)
      Nakamura M, Chiba_K., Nishizawa T, Maruiwa H, Matsumoto M, Toyama Y
    • Journal Title

      J Neurosurg 100

      Pages: 241-244

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Retrospective study of surgery-related outcomes in patients with syringomyelia associated with Chiari I malformation : clinical significance of changes in the size and location of syrinx on pain relief.2004

    • Author(s)
      Nakamura M., Chiba K., Nishizawa T, Maruiwa H, Matsumoto M, Toyama Y
    • Journal Title

      J Neurosurg(Spine 3) 100

      Pages: 241-244

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Postoperative changes of spinal curvature and range of motion in adult patients with cervical spinal cord tumors -Analysis of 51 cases and review of the literature-.2004

    • Author(s)
      Asazuma T, Nakamura M, Matsumoto M, Chiba K, Toyama Y.
    • Journal Title

      J Spinal Disord Tech 17

      Pages: 178-182

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Development of a New Zealand White rabbit model of pseudoarthrosis repair and evaluation of the potential role of OP-1 to overcome pseudarthrosis.2004

    • Author(s)
      Grauer J.N., Vaccaro A.R., Kato M., Kwon BK., Beiner J.M., Patel T., Hilibrand AS., Chiba K., Albert T.J.
    • Journal Title

      Spine 29

      Pages: 1405-1412

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Long-term results(minimal five years) of expansive open-door laminoplasty for ossification of the posterior longitudinal ligament of the cervical spine.2004

    • Author(s)
      Ogawa Y., Chiba K., Matsumoto M., Nakamura M., Takaishi H., Hirabayashi H., Hirabayashi K., Toyama Y.
    • Journal Title

      J Neurosurg Spine 2

      Pages: 168-174

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Synaptic blockade plays a major role in the neural disturbance of experimental spinal cord compression.2003

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

      J Neurotrauma 20

      Pages: 1365-1376

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Recombinant osteogenic protein-i upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells.2003

    • Author(s)
      Masuda K., Takegami K., An H., Kumano F., Chiba_K., Andersson G.B.J., Schmid T., Thonar E.J.M-A
    • Journal Title

      J Orthop.Res 21

      Pages: 922-930

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Relationship between alignment of upper and lower cervical spine in asymptomatic individuals.2003

    • Author(s)
      Nojiri K., Matsumoto M., Chiba_K., Maruiwa H., Nakamura M., Nishizawa T., Toyama Y.
    • Journal Title

      J Neurosurg. 99

      Pages: 80-83

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Changes of cervical spinal cord and cervical canal with age in asymptomatic subjects2003

    • Author(s)
      Ishikawa M., Matsumoto M., Fujimura Y., Chiba K., Toyama Y.
    • Journal Title

      Spinal Cord 41

      Pages: 159-163

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Relationship between alignment of upper and lower cervical spine in asymptomatic individuals.2003

    • Author(s)
      Nojiri K., Matsumoto M., Chiba K.Maruiwa H., Nakamura M., Nishizawa T., Toyama Y.
    • Journal Title

      J Neurosurg(Spine 1) 99

      Pages: 80-83

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Recombinant osteogenic protein-1 upregulates extracellular matrix metabolism by rabbit annulus fibrosus and nucleus pulposus cells.2003

    • Author(s)
      Masuda K., Takegami K., An H., Kumano F., Chiba K., Andereson G.B.J., Schmid T..Thonar E.J.M-A.
    • Journal Title

      J Orthop Re 21

      Pages: 922-930

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

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Published: 2006-07-11  

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