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analysis of the mechanism of bone and joint destruction by beta2-microglobulin amyloid deposion

Research Project

Project/Area Number 26860236
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Human pathology
Research InstitutionUniversity of Fukui

Principal Investigator

Okoshi Tadakazu  福井大学, 医学部, 助教 (90362037)

Research Collaborator NAIKI Hironobu  福井大学, 医学部, 教授 (10227704)
HASEGAWA Kazuhiro  福井大学, 医学部, 助教 (60324159)
OZAWA Daisaku  福井大学, テニュアトラック推進本部, 助教 (60554524)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsアミロイドーシス / β2-ミクログロブリン / 細胞毒性 / 滑膜細胞 / エンドサイトーシス / リソソーム / 滑膜線維芽細胞 / 血液透析 / 透析アミロイドーシス
Outline of Final Research Achievements

In dialysis-related amyloidosis, β2-microglobulin (β2-m) amyloid fibrils deposit in the osteoarticular tissue, leading to carpal tunnel syndrome and destructive arthropathy, but the mechanism by which these amyloid fibrils destruct bone and joint tissue is not fully understood. In this study, we assessed the cytotoxic effect ofβ2-m amyloid fibrils on the cultured rabbit synovial fibroblasts. β2-m amyloid fibrils exerted the toxic effect on the synovial fibroblasts. When the cells were incubated with amyloid fibrils, many endosomes/lysosomes filled with amyloid fibrils were observed. Moreover, some endosomal/lysosomal membranes were disrupted by intravesicular fibrils, leading to the leakage of the fibrils into the cytosol and adjacent to mitochondria. Inhibition of endocytosis by cytochalasin D attenuated the toxicity of amyloid fibrils. These results suggest that endocytosed β2-m amyloid fibrils induce necrosis and apoptosis by disrupting endosomal/lysosomal membranes.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Molecular pathogenesis ofhuman amyloidosis: Lessons from β2 -microglobulin-related amyloidosis.2016

    • Author(s)
      Naiki H, Okoshi T, Ozawa D, Yamaguchi I, Hasegawa K.
    • Journal Title

      Pathol Int.

      Volume: ;66(4) Issue: 4 Pages: 193-201

    • DOI

      10.1111/pin.12394

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] アミロイドーシスの発症メカニズムについて2016

    • Author(s)
      大越忠和、小澤大作、山口格、長谷川一浩、内木宏延
    • Journal Title

      病理と臨床

      Volume: 34 Pages: 454-459

    • Related Report
      2015 Annual Research Report
  • [Journal Article] アミロイド線維の形成、沈着と臓器障害の分子機構2016

    • Author(s)
      大越忠和、内木宏延
    • Journal Title

      医学のあゆみ

      Volume: 258

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Endocytosed β2-Microglobulin Amyloid Fibrils Induce Necrosis and Apoptosis of Rabbit Synovial Fibroblasts by Disrupting Endosomal/Lysosomal Membranes: A Novel Mechanism on the Cytotoxicity of Amyloid Fibrils.2015

    • Author(s)
      Okoshi T, Yamaguchi I, Ozawa D, Hasegawa K, Naiki H
    • Journal Title

      PLoS One

      Volume: 10 Issue: 9 Pages: e0139330-e0139330

    • DOI

      10.1371/journal.pone.0139330

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 滑膜線維芽細胞に対するβ2‐ミクログロブリンアミロイド線維の細胞毒性メカニズムの解析2014

    • Author(s)
      大越忠和、山口格、長谷川一浩、小澤大作、内木宏延
    • Organizer
      第2回日本アミロイドーシス研究会
    • Place of Presentation
      KKRホテル東京(東京都千代田区)
    • Year and Date
      2014-08-22
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-22  

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