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THE ROLE OF NITRIC OXIDE DURING THE PROCESS OF INTERVERTEBRAL DISC DEGENERATION AND PREVENTION OF DISC DEGENERATION USING i-NOS ANTI SENSE OLIGONUCLEOTIDE

Research Project

Project/Area Number 12671401
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionTOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY

Principal Investigator

ISHIHARA Hirokazu  Toyama Medical and Pharmaceutical University, University Hospital, Assistant Professor, 附属病院, 講師 (30242499)

Co-Investigator(Kenkyū-buntansha) KAWAGUCHI Yoshiharu  Toyama Medical and Pharmaceutical University, Faculty of Medicine, Instructor, 医学部, 助手 (00262527)
OSADA Ryusuke  Toyama Medical and Pharmaceutical University, University Hospital, Instructor, 附属病院, 助手 (40293310)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
KeywordsNitric Oxide / Proteoglycan / Intervertebral disc metabolism / i-NOS / アンチセンスオリゴヌクレオチド / NO (Nitric Oxide) / プロオテオグリカン / 椎間板代謝 / i-NOS / プロテオグリカン
Research Abstract

The intervertebral disc degeneration is the major cause of disc dysfunction and low back pain. Many factors are known to influence intervertebral disc degeneration. Nitric Oxide (NO) is an inorganic, gaseous free radical and identified as the elusive blood vessel relaxing factor. We have clarified that the role of NO in disc metabolism and the effects of i-NOS anti-sense oligonucleotide that control NO production to prevent experimental rabbit disc degeneration model. The degenerated rabbit intervertebral disc spontaneously produced NO and NO inhibited proteoglycan synthesis and increased the production of Matrix metalloproteinase-3 in the disc. I-NOS anti-sense oligonucleotide inhibited proteoglycan loss and matrix metalloproteinase production.
Histologically, i-NOS anti-sense oligonucleotide inhibited the reduction of Safranin-O staining and production of annulus fibrosus tear during the degeneration process.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Ishihara H., et al.: "Effects of low oxygen concentrations and metabolic inhibitors 刧on proteoglycan and protein synthesis rates in the intervertebral disc"J Orthop Res. 17・6. 829-835 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawaguchi Y., Ishihara H., et al.: "Association between an aggrecan gene polymorphism in lumbar disc degeneration"Spine. 24・23. 2456-2460 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Liu G., Ishihara H., Osada R., et al.: "Nitric oxide mediates the change of ptoteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure"Spine. 26・2. 385-389 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara H., Osada R., Kawaguchi Y., et al.: "Minimum 10 year follow-up study of anterior interbody fusion for isthmic spondylolisthesis"J Spinal Disord. 14・2. 91-99 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara H., Kawaguchi Y., Osada R., et al.: "Prediction of neurological outcome in patients with spinal cord injury by using hyperbaric oxygen therapy"J Orthopasedic Sci. 6. 385-389 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 長田龍介, 石原裕和: "椎間板細胞における増殖因子の役割"脊椎脊髄. 14. 271-274 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 石原裕和, 柳 根哲, 他: "メカニカルバイオロジーからみた椎間板変性のメカニズム"脊椎脊髄. 14・4. 271-274 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara H., Liu G., et al.: "Intervertebral disc metabolism under mechanical load ; The role of extracellular physical factors"Preceedings of 4^<th> World Congress on Biomechanics. (CD-ROM). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara H, et al.: "Effects of low oxygen, concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc."J Orthop Res. 17・6. 829-835 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawaguchi Y, Ishihara H, et al.: "Association between an aggrecan gene polymorphism in lumbar disc degeneration."Spine. 24・23. 2456-2460 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Liu G, Ishihara H, Osada R, et al.: "Nitric oxide mediates the change of proteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure."Spine. 26・2. 134-141 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara H, Osada R, Kawaguchi Y, et al.: "Minimum 10 year follow-up study of anterior interbody fusion for isthmic spondylolisthesis."J Spinal Disord. 14・2. 91-99 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara H, Kawaguchi Y, Osada R, et al.: "Prediction of neurologic outcome in patients with spinal Cord injury using hyperbaric oxygen therapy."J Orthop Sci. 6. 385-389 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara H., Liu G., et al.: "Intervertebral disc metabolism under mechanical load ; The role of extracellular physical factors."Preceedings of 4^<th> World Congress on Biomechanics (CD-ROM). (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishihara H., Liu G., et al.: "Intervertebral disc metabolism under mechanical load : The role of extracellular physical factors"Proceedings of VIth World Congress on Biomechanics. (CD-ROM). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishihara H., Kawaguchi Y., Osada R., et al.: "Prediction of neurological outcome in patients with spinal cord injury by using hyperbaric oxygen therapy"J Orthopaedic Sci. 6. 385-389 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishihara H., Osada R., et al.: "Minimum 10 year follow-up study of anterior interbody fusion for isthmic spondylolisthesis"J Spinal Disord. 14. 91-100 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Liu G., Ishihara H., et al.: "Nitric oxide mediates the change of ptoteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure"Spine. 26. 134-141 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 石原裕和, 柳 根哲, 他: "メカニカルバイオロジーからみた椎間板変性のメカニズム"脊椎脊髄. 14. 271-274 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishihara H., et al.: "Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk"J Appl Physiol. 80. 839-846 (1996)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishihara H., et al.: "Proteoglycan synthesis in the intervertebral disk nucleus : the role of extracellular osmolarity"Am J Physiol. 272(Cell Physiol 41). C1499-C1506 (1997)

    • Related Report
      2001 Annual Research Report
  • [Publications] Handa T., Ishihara H., et al.: "Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc"Spine. 22. 1085-1091 (1997)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishihara H., et al.: "Effects of low oxygen concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc"J Orhop Res. 17. 829-835 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Liu G., Ishihara H., et al.: "Nitric oxide mediates the change of ptoteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure"Spine. 26. 134-141 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 石原裕和, 柳 根哲, 他: "メカニカルバイオロジーからみた椎間板変性のメカニズム"脊椎脊髄. 14. 271-274 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishihara H, et al: "Effects of hydrostatic pressure on matrix synthesis in different regions of the intervertebral disk."J Appl Physiol. 80:. 839-846 (1996)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishihara H, et al: "Proteoglycan synthesis in the intervertebral disk nucleus : the role of extracellular osmolarity."Am J Physiol. 272. C1499-C1506 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] Handa T,Ishihara H, et al: "Effects of hydrostatic pressure on matrix synthesis and matrix metalloproteinase production in the human lumbar intervertebral disc."Spine. 22:. 1085-1091 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishihara H, et al: "Effects of low oxygen concentrations and metabolic inhibitors on proteoglycan and protein synthesis rates in the intervertebral disc."J Orthop Res. 17:. 829-835 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Liu G,Ishihara H, et al: "Nitric oxide mediates the change of ptoteoglycan synthesis in the human lumbar intervertebral disc in response to hydrostatic pressure."Spine. 26:. 134-141 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 長田龍介,石原裕和: "椎間板細胞における増殖因子の役割"脊椎脊髄. 14:. 211-215 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 大島博,石原裕和: "椎間板の生理学的生物学的特性「NEW MOOK整形外科2」"金原出版、東京. 10-17 (1997)

    • Related Report
      2000 Annual Research Report
  • [Publications] 石原裕和: "メカニカルバイオロジーからみた椎間板変性のメカニズム"三輪書店、東京(印刷中). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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