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Comprehensive analysis of osteocyte gene expression induced by TNF-a

Research Project

Project/Area Number 21K10178
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57070:Developmental dentistry-related
Research InstitutionTohoku University

Principal Investigator

Ogawa Saika  東北大学, 歯学研究科, 大学院非常勤講師 (60882397)

Co-Investigator(Kenkyū-buntansha) 溝口 到  東北大学, 歯学研究科, 教授 (20200032)
北浦 英樹  東北大学, 歯学研究科, 准教授 (60295087)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords骨細胞 / TNF / 破骨細胞 / TNF-α / RNAシークエンス
Outline of Research at the Start

骨細胞特異的に蛍光を発するC57BL/6-Tg(Dmp1-Topaz)1Ikal/Jマウスの頭蓋骨から、FACSを使用してほぼ100%純粋な骨細胞の単離を行う。この骨細胞にTNF-αを作用させ、TNF-αによる骨細胞への影響を遺伝子の発現をRNAシークエンスで網羅的に解明する。RNAシークエンス解析で得られた増加制御および減少制御された遺伝子の骨細胞での発現の確認を行う。TNF-αが骨細胞に影響し高発現した遺伝子のRANKL発現へ影響の解析を行う。

Outline of Final Research Achievements

The purpose of this study is to comprehensively analyze gene expression when TNF-a acts on osteocytes and elucidate its effects on osteoclast formation. Osteocytes were isolated using a cell sorter from 5-6 day old DMP1-Topaz mice whose osteocytes have green fluorescence. When osteocytes were cultured with TNF-a and an increase in gene expression of the chemokine Cxcl10 was found by RNA sequencing. CXCL10 did not affect osteoclast formation but promoted the migration of osteoclast precursor cells. It was suggested that CXCL10, which is expressed by osteocytes due to TNF-a, increases osteoclast formation by promoting the migration of osteoclast precursor cells.

Academic Significance and Societal Importance of the Research Achievements

TNF-aが骨細胞に作用した際の遺伝子発現を網羅的に調べた報告はなく、特に高純度な骨細胞に対しては、報告は非常に少ない。そのため、炎症性サイトカインであるTNF-aの骨細胞に対する作用を明らかにすることは重要な研究である。また、骨細胞の骨代謝に関する未知の作用が明らかできる可能性やさらに骨代謝だけでなく他の様々な生体反応への作用を明らかにできる可能性があり重要であると考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2023 2022

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

  • [Journal Article] Docosahexaenoic acid inhibits TNF-α-induced osteoclast formation and orthodontic tooth movement through GPR1202023

    • Author(s)
      Jinghan Ma, Hideki Kitaura, Saika Ogawa, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Yasuhiko Nara, Adya Pramusita, Ria Kinjo, Kayoko Kanou, Akiko Kishikawa, Atsuhiko Ichimura, Itaru Mizoguchi
    • Journal Title

      Front Immunol.

      Volume: eCollection 2022. Pages: 929690-929690

    • DOI

      10.3389/fimmu.2022.929690

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Micro-Osteoperforations Induce TNF-α Expression and Accelerate Orthodontic Tooth Movement via TNF-α-Responsive Stromal Cells2022

    • Author(s)
      Kinjo Ria、Kitaura Hideki、Ogawa Saika、Ohori Fumitoshi、Noguchi Takahiro、Marahleh Aseel、Nara Yasuhiko、Pramusita Adya、Ma Jinghan、Kanou Kayoko、Mizoguchi Itaru
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 6 Pages: 2968-2968

    • DOI

      10.3390/ijms23062968

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2021-04-28   Modified: 2025-01-30  

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