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Investigation of chromatic remodeling in osteoclast function for therapeutic targeting of bone remodeling balance

Research Project

Project/Area Number 19K10044
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionHokkaido University (2020-2022)
Ehime University (2019)

Principal Investigator

Lee Ji-Won  北海道大学, 歯学研究院, 助教 (70711274)

Project Period (FY) 2019-04-01 – 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 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordschromatin remodeler / BAF155 / osteoclast / bone / Osteoclast / Baf155 / Chromatin remodeler / sexual dimorphism / Bone / SWI/SNF / Smarcc1 / Histomorphometry / Rank / Lysosome
Outline of Research at the Start

Our current observation on CCR5 as a co-receptor of HIV, firstly shows functionally distinctive bone phenotype, and suggest ‘Drug-repositioning’ effect of CCR5-targeted therapy, indicating not only HIV blocker but also protector against bone-destructive conditions. In our ongoing experiments, we have identified CCR5-mediated protein targets of BAF complex that may affect to osteoclast function. In here, we will seek for the mechanisms of chromatin remodeling complex mediating regulation of osteoclast function for anabolic bone remodeling by taking genome-wide approaches.

Outline of Final Research Achievements

This study investigated the functional role of Baf155, an epigenetic chromatin remodeler in osteoclasts. In this fiscal year, we found that the effect of Baf155 cKO mice on bone mineral density (BMD) differed between sexes, even at the same age. Interestingly, microCT analysis of 8-week-old mice showed an increase in BMD only in male mice, but there was no difference in BMD at 16 weeks of age. Conversely, in 8-week-old female mice, there was no difference in BMD compared to the control group, but at 16 weeks of age, BMD parameter significantly increased in Baaf155 cKO. Our results suggest that the epigenetic regulation of the chromatin regulator Baf155 on osteoclasts and bone differs according to sexual dimorphism.

Academic Significance and Societal Importance of the Research Achievements

Age-related bone resorption diseases are common in women. However, there are no gender-specific clinical trials or drug guidelines. From a gender difference medical perspective, the accumulation of pathophysiological evidence is important.

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2023 2022 2021 2020

All Journal Article (10 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 9 results,  Open Access: 9 results) Presentation (1 results)

  • [Journal Article] Association between an increased serum CCL5 level and pathophysiology of degenerative joint disease in the temporomandibular joint in females2023

    • Author(s)
      H Watanabe, T Iori, Ji-Won Lee, T Kajii, A Takakura, T Takao-Kawabata, Y Kitagawa, Y Maruoka, T Iimura
    • Journal Title

      International journal of molecular sciences

      Volume: 24 Issue: 3 Pages: 2775-2775

    • DOI

      10.3390/ijms24032775

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evolution of multiple comics approaches to define pathophysiology of pediatric acute respiratory distress syndrome2022

    • Author(s)
      Jane E Whitney, In-Hee Lee, Ji-Won Lee, Sek Won Kong
    • Journal Title

      Elife

      Volume: 11

    • DOI

      10.7554/elife.77405

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The Lipid-Binding Defective Dynamin 2 Mutant in Charcot-Marie-Tooth Disease Impairs Proper Actin Bundling and Actin Organization in Glomerular Podocytes2022

    • Author(s)
      Hamasaki Eriko、Wakita Natsuki、Yasuoka Hiroki、Nagaoka Hikaru、Morita Masayuki、Takashima Eizo、Uchihashi Takayuki、Takeda Tetsuya、Abe Tadashi、Lee Ji-Won、Iimura Tadahiro、Saleem Moin A、Ogo Naohisa、Asai Akira、Narita Akihiro、Takei Kohji、Yamada Hiroshi
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 10 Pages: 884509-884509

    • DOI

      10.3389/fcell.2022.884509

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Histone H3K27 demethylase, Utx, regulates osteoblast-to-osteocyte differentiation2022

    • Author(s)
      Xia Yuhan、Ikedo Aoi、Lee Ji-Won、Iimura Tadahiro、Inoue Kazuki、Imai Yuuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 590 Pages: 132-138

    • DOI

      10.1016/j.bbrc.2021.12.102

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expansion of the osteocytic lacunar-canalicular system involved in pharmacological action of PTH revealed by AI-driven fluorescence morphometry in female rabbits2022

    • Author(s)
      A Takakura, T Sato, Ji-Won Lee, K Hirano, R Takao-Kawabata, T Ishizuka, T Iimura
    • Journal Title

      Scientific reports

      Volume: 12 Issue: 1

    • DOI

      10.1038/s41598-022-20793-5

    • Related Report
      2022 Annual Research Report
  • [Journal Article] A quantitative analysis of bone lamellarity and bone collagen linearity induced by distinct dosing and frequencies of teriparatide administration in ovariectomized rats and monkeys2021

    • Author(s)
      Sato Takanori、Takakura Aya、Lee Ji-Won、Tokunaga Kazuaki、Matsumori Haruka、Takao-Kawabata Ryoko、Iimura Tadahiro
    • Journal Title

      Microscopy

      Volume: 70 Issue: 6 Pages: 498-509

    • DOI

      10.1093/jmicro/dfab020

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic variation analyses indicate conserved SARS‐CoV‐2-host interaction and varied genetic adaptation in immune response factors in modern human evolution2021

    • Author(s)
      Lee Ji‐Won、Lee In‐Hee、Sato Takanori、Kong Sek Won、Iimura Tadahiro
    • Journal Title

      Development, Growth & Differentiation

      Volume: 63 Issue: 3 Pages: 219-227

    • DOI

      10.1111/dgd.12717

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Two macrophages, osteoclasts and microglia: from development to pleiotropy2021

    • Author(s)
      Lee Ji-Won、Lee In-Hee、Iimura Tadahiro、Kong Sek Won
    • Journal Title

      Bone Research

      Volume: 9 Issue: 1 Pages: 11-11

    • DOI

      10.1038/s41413-020-00134-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A survey of genetic variants in SARS-CoV-2 interacting domains of ACE2, TMPRSS2 and TLR3/7/8/ across populations2020

    • Author(s)
      In-Hee Lee, Ji-Won Lee, Sek Won Kong
    • Journal Title

      Infection, Genetics and Evolution

      Volume: 85 Pages: 104507-104507

    • DOI

      10.1016/j.meegid.2020.104507

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Teriparatide relieves ovariectomy-induced hyperalgesia in rats, suggesting the involvement of functional regulation in primary sensory neurons by PTH-mediated signaling.2020

    • Author(s)
      Tanaka T, Takao-Kawabata R, Takakura A, Shimazu Y, Nakatsugawa M, Ito A, Lee JW, Kawasaki K, Iimura T.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 5346-5346

    • DOI

      10.1038/s41598-020-62045-4

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] SARS-CoV-2の相互作用分子ACE2, TMPRSS2およびTLR3/7/8における人口集団の遺伝的変異調査2021

    • Author(s)
      李 智媛、In-Hee Lee, Sek Won Kong, 飯村 忠浩
    • Organizer
      日本薬理学会
    • Related Report
      2021 Research-status Report

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Published: 2019-04-18   Modified: 2024-12-25  

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