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Association of innate immune abnormalities with the development and collapse of idiopathic osteonecrosis of the femoral head.

Research Project

Project/Area Number 20K17984
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionHokkaido University

Principal Investigator

Shimizu Tomohiro  北海道大学, 大学病院, 助教 (60784246)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords特発性大腿骨頭壊死症 / 好中球 / 全身MRI / 好中球トラップ / 自然免疫異常 / 多発骨壊死 / 自然免疫
Outline of Research at the Start

特発性大腿骨頭壊死症(ONFH)は国の定める難病であり、現在のところ発生及び圧潰のメカニズムは十分に解明されていない。本研究の目的は、①疫学的にONFHと関連するSLEやネフローゼ症候群の発症に深い関わりを持つことが近年明らかとなった好中球トラップ(NETs)に注目し、ONFH発生とNETsの関連性を明らかにすること②圧潰のメカニズムを骨代謝アプローチにより関連性を調査することである。本研究は、人工股関節全置換術を行うONFH症例の臨床サンプルを用いて自然免疫異常とONFHの発生・圧潰の関連を調査する前向き観察研究である。

Outline of Final Research Achievements

Whole-body MRI proved to be a useful screening for osteonecrosis in idiopathic osteonecrosis of the femoral head, as it identified asymptomatic osteonecrosis compared to bone scintigraphy.
In all cases of idiopathic osteonecrosis of the femoral head, histological expression of NETs was confirmed in the soft tissues of the periprosthetic femoral head, and when a rat model with strong NETs expression was created, expression of NETs was confirmed in the periprosthetic femoral head tissue as in clinical specimen samples. In addition, osteonecrosis and positive expression of HIF1α, a marker of ischemia, could be partially confirmed. This could not be confirmed in the controls. These findings suggest that the expression of NETs is associated with the development of osteonecrosis of the femoral head.

Academic Significance and Societal Importance of the Research Achievements

特発性大腿骨頭壊死症(ONFH)は国の定める難病であり、現在のところ発生及び圧潰のメカニズムは十分に解明されていない。本研究の目的は、疫学的にONFHと関連するSLEやネフローゼ症候群の発症に深い関わりを持つことが近年明らかとなった好中球トラップ(NETs)に注目し、ONFH発生とNETsの関連性を明らかにすることである。本研究は、人工股関節全置換術を行うONFH症例の臨床サンプルを用いて自然免疫異常とONFHの発生の関連を調査する前向き観察研究である。本研究によりONFHの発生メカニズムの一部が解明されれば、発生・圧潰予測因子の解明や予防法の確立につながり治療成績向上に繋がる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (3 results)

All 2022 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results)

  • [Journal Article] Inflammasome Activation in the Hip Synovium of Rapidly Destructive Coxopathy Patients and Its Relationship with the Development of Synovitis and Bone Loss2022

    • Author(s)
      Yokota Shunichi、Shimizu Tomohiro、Matsumae Gen、Ebata Taku、Alhasan Hend、Takahashi Daisuke、Terkawi Mohamad Alaa、Iwasaki Norimasa
    • Journal Title

      The American Journal of Pathology

      Volume: 192 Issue: 5 Pages: 794-804

    • DOI

      10.1016/j.ajpath.2022.02.003

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of whole-body modalities for diagnosis of multifocal osteonecrosis?a pilot study2021

    • Author(s)
      Yokota Shunichi、Sakamoto Keita、Shimizu Yukie、Asano Tsuyoshi、Takahashi Daisuke、Kudo Kohsuke、Iwasaki Norimasa、Shimizu Tomohiro
    • Journal Title

      Arthritis Research & Therapy

      Volume: 23 Issue: 1 Pages: 83-83

    • DOI

      10.1186/s13075-021-02473-3

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of Neutrophil Extracellular Traps with the Development of Idiopathic Osteonecrosis of the Femoral Head2020

    • Author(s)
      Nonokawa Mayu、Shimizu Tomohiro、Yoshinari Miku、Hashimoto Yamato、Nakamura Yusuke、Takahashi Daisuke、Asano Tsuyoshi、Nishibata Yuka、Masuda Sakiko、Nakazawa Daigo、Tanaka Satoshi、Tomaru Utano、Iwasaki Norimasa、Ishizu Akihiro
    • Journal Title

      The American Journal of Pathology

      Volume: 190 Issue: 11 Pages: 2282-2289

    • DOI

      10.1016/j.ajpath.2020.07.008

    • NAID

      120007168180

    • Related Report
      2020 Research-status Report
    • Peer Reviewed

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Published: 2020-04-28   Modified: 2024-01-30  

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