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APOPTOSIS OF CELLS OF NUCLEUS PULPOSUS AND ACTIVATION MECHANISM OF INTERCELLULAR SIGNALING DURING DEGENERATION OF INTERVERTEBRAL DISC

Research Project

Project/Area Number 13671523
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MATSUNAGA Shunji  KAGOSHIMA UNIVERSITY, UNIVERSITY HOSPITAL FACULTY OF MEDICINE AND DENTISTRY, ASSISTANT PROFESSOR, 医学部・歯学部附属病院, 講師 (90229500)

Co-Investigator(Kenkyū-buntansha) KOMIYA Setsuro  KAGOSHIMA UNIVERSITY, GRADUATE SCHOOL OF MEDICAL AND DENTAL SCIENCES, PROFESSOR, 大学院・医歯学総合研究科, 教授 (30178371)
SUZUKI Shusaku  KAGOSHIMA UNIVERSITY, FACULTY OF AGRICULTURE, ASSOCIATE PROFESSOR, 農学部, 教授 (70041663)
YONE Kazunori  KAGOSHIMA UNIVERSITY, GRADUATE SCHOOL OF MEDICAL AND DENTAL SCIENCES, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (40182844)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordssenescence-accelerated mice / intervertebral disc / cytokines / apoptosis / intercellular signaling / 変性 / TGF-β / 分子生物学 / 老化 / 髄核細胞 / 細胞内シグナル伝達
Research Abstract

We previously conducted immunohistological studies of changes in TGF-β and BMP expression in nucleus pulposus cells following degeneration of the intervertebral disc. These studies suggested that changes in TGF-β expression are associated with apoptosis of cells. Following this finding, the present study was undertaken to clarify the mechanism of aging from the viewpoint of apoptosis, using molecular biological methods. The study involved a senescence-accelerated mouse strain (SAM-P/6) as the animal model, allowing observation of aging in a short time period. During last year, we removed the intervertebral discs of the cervical spine from male senescence-accelerated mice at ages 4, 8, 12, 16, 20, 24, 28, 32 and 50 weeks and examined immunohistologically the expression of TGF-β1, -β2, -β3 and their receptors in the discs' nucleus pulposus cells. The study revealed that as age advanced the expression of nucleus pulposus cell TGF-β1, -β2, -β3 and their receptors decreased, reaching almost … More zero at age 50 weeks and was accompanied by a decrease in the number of nucleus pulposus cells. This year, we conducted an experiment designed to demonstrate that such a decrease in nucleus pulposus cells is due to apoptosis. In this study, nucleus pulp cells of senescence-accelerated mice were stained positively using the TUNEL method and were found to already have caspase activity at age 32 weeks, suggesting that apoptosis had begun at this age. Morphological observation of the nuclei of the cells with an electron microscope also revealed apoptotic changes. The changes suggesting apoptosis were more marked at age 50 weeks.
In 2003, we conducted immunohistological studies of ASK1, JNK and p38 aimed at clarifying the mechanism for intracellular signal transduction associated with apoptosis during degeneration of intervertebral discs. As the disc degenerated, the expression of ASK1, JNK and p38 in nucleus pulposus cells was noted, but it was also observed in the control group. Thus, it was not possible to clarify the mechanism for intracellular signal transduction associated with apoptosis. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] I.Yamaura, K.Yone, et al.: "Mechanism of destractive pathologic changes in spinal cord under clonic mechanical compression."Spine. 27. 21-26 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Matsunaga, S.Nagano, et al.: "Age-related chages in expression of transforming growth factor-β and receptors in cells of intervertebral discs."J.Neurosurg.. 98. 63-67 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Maeda, M.Hayashi, S.Komiya, et al.: "Endogenous TGF-β signaling supressed maturation of osteoblastic mesenchymal cells."The EMBO J. 23. 1-12 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Y.Yazaki, S, Matsunaga, et al.: "Localization of bone morphogenetic proteins and there intercellular signaling compornents(Smads) in the growth plate. In-Biochemical and Health Research"IOS Press. 259-264 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] I.Yamaura, K.Yone, S.Nakahara, T.Nagamine, H.Baba, K.Uchida, S.Komiya: "Mechanism of destructive pathologic changes in spinal cord under chronic mechanical compression."Spine. 27. 21-26 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Matsunaga, S.Nagano, T.Onishi, N.Morimoto, S.Suzuki, S.Komiya: "Age-related changes in expression of transforming growth factor-β and receptors in cells of intervertebral discs."J Neurosurg. 98. 63-67 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Maeda, M.Hayashi, S.Komiya, T.Imamura, K.Miyazono: "Endogenous TGF-signaling suppressed maturation of osteoblastic mesenchymal cells."The EMBO J. 1-12 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shunji Matsunaga: "Age-related changes in expression of transforming growth factor-β and receptors in cells of intervertebral discs"J Neurosurg. 98. 63-67 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 松永 俊二: "椎間板変性とサイトカイン"日本整形外科学会雑誌. 77. S924 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shunji Matsunaga: "Age-related changes in expression of transforming growth factor-β and receptors in cells of intervertebral discs"J Neurosurg. 98. 63-67 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 松永俊二: "SAM椎間板細胞におけるTGF-βおよび受容体の発現と変化"第17回老化促進マウス(SAM)研究協議会抄録集. 23 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagano S, Matsunaga S, Takae R, Morimoto N, Suzuki S, Komiya S: "Immunolocalization of transforming growth factor-betas and their receptors in the intervertebral disk of senescence-accelerated mouse"International Journal of Oncology. 17. 461-466 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 松永俊二, 永野 聡, 大西敏之, 小宮節郎, 森本典夫, 鈴木秀作: "SAM椎間板細胞におけるTGF-βおよび受容体の発現の変化"第17回老化マウス(SAM)研究協議会抄録集. 23-24 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 永野 聡, 松永俊二, 石堂康弘, 小宮節郎: "免疫組織染色におけるマイクロウエーブを用いた抗原賦活法の効果"日本生体電気刺激研究会誌. 14. 15-18 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagano S, Matsunaga S, Yamamoto T, Yone K, Sakou, Komiya S: "Immunolocalization of transforming growth factor-betas and their receptors in the intervertebral disk of cervical spine"Proceedings of Fourth Combined Meeting of the Orthopawedic research Societies of the USA, Canada, Europe, and Japan. 45-46 (2001)

    • Related Report
      2001 Annual Research Report

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

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