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The exploration of exosome involvement in skeletal abnormalities induced by dysregulation of zinc homeostasis

Research Project

Project/Area Number 18K09540
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionShowa University

Principal Investigator

Yasuhara Rika  昭和大学, 歯学部, 講師 (20453649)

Co-Investigator(Kenkyū-buntansha) 川嶋 章弘  昭和大学, 医学部, 講師 (10783376)
田中 準一  昭和大学, 歯学部, 講師 (40710166)
美島 健二  昭和大学, 歯学部, 教授 (50275343)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords骨格形成 / 軟骨 / 細胞・組織 / 遺伝子 / 骨格成長 / 亜鉛トランスポーター / エキソソーム / シグナル伝達
Outline of Final Research Achievements

Abnormal zinc metabolism leads to skeletal and immune abnormalities. The purpose of this research project was to elucidate the pathogenesis of skeletal abnormalities caused by disruption of zinc homeostasis. ZIP10 (zinc transporter) deficient cells, which are responsible for intracellular regulation of zinc, showed higher variation in bone metabolism-related gene clusters and gene clusters related to vesicles and exosomes compared to wild-type cells. Isolated exosomes expressed mesenchymal cell-specific markers in addition to known exosome markers, and DIA proteome analysis identified 1798 proteins involved in the developmental process in isolated exosomes of ZIP10-deficient cells. Zinc may regulate bone metabolism-related cell differentiation via exosomes.

Academic Significance and Societal Importance of the Research Achievements

必須微量因子である亜鉛の代謝異常は骨格異常や骨粗鬆症、さらに免疫力の低下をきたし、老化に関わる事が示唆されている。亜鉛の細胞内濃度は亜鉛トランスポーターを介して調節される。本研究課題は、ZIP10欠損マウスを作製し、亜鉛欠乏した骨関連細胞で発現する遺伝子をRNA-sequence法を用いて網羅的に解析した。さらに、細胞からエキソソームを回収し、LC-MS/MSを用いてエキソソームに含まれるタンパク質の解析を行った。亜鉛のエキソソームに対する作用の解明は、報告が少なく、本研究課題の成果は、骨格形成のみならず、関節疾患の病態メカニズムや治療法開発に新たな知見と理解をもたらすと考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2022 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 8 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Assessment of MEF2C as a novel myoepithelial marker using normal salivary gland and pleomorphic adenoma: An immunohistochemical study2022

    • Author(s)
      Takakura Ikuko、Kujiraoka Satoko、Yasuhara Rika、Tanaka Junichi、Ide Fumio、Mishima Kenji
    • Journal Title

      Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology

      Volume: NA Issue: 4 Pages: 523-530

    • DOI

      10.1016/j.ajoms.2022.01.001

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Induction of salivary gland-like cells from epithelial tissues transdifferentiated from mouse embryonic fibroblasts2022

    • Author(s)
      Katada Ryogo、Tanaka Junichi、Takamatsu Koki、Hata Kenji、Yasuhara Rika、Ohnuma Shintaro、Takakura Ikuko、Nishimura Riko、Shirota Tatsuo、Mishima Kenji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 586 Pages: 55-62

    • DOI

      10.1016/j.bbrc.2021.11.064

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vitro monitoring of HTR2A-positive neurons derived from human-induced pluripotent stem cells2021

    • Author(s)
      Nakai Kento、Shiga Takahiro、Yasuhara Rika、Sarkar Avijite Kumer、Abe Yuka、Nakamura Shiro、Hoashi Yurie、Kotani Keisuke、Tatsumoto Shoji、Ishikawa Hiroe、Go Yasuhiro、Inoue Tomio、Mishima Kenji、Akamatsu Wado、Baba Kazuyoshi
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 15437-15437

    • DOI

      10.1038/s41598-021-95041-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sox9 function in salivary gland development.2021

    • Author(s)
      Tanaka J, Takamatsu K, Yukimori A, Kujiraoka S, Ishida S, Takakura I, Yasuhara R, Mishima K.
    • Journal Title

      J Oral Biosci.

      Volume: 63(1) Issue: 1 Pages: 8-13

    • DOI

      10.1016/j.job.2021.01.005

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Engraftment potential of maternal adipose-derived stem cells for fetal transplantation2020

    • Author(s)
      Kawashima Akihiro、Yasuhara Rika、Akino Ryosuke、Mishima Kenji、Nasu Michiko、Sekizawa Akihiko
    • Journal Title

      Heliyon

      Volume: 6 Issue: 3 Pages: 1-9

    • DOI

      10.1016/j.heliyon.2020.e03409

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cytokine profiles in maternal serum are candidates for predicting an optimal timing for the delivery in early‐onset fetal growth restriction2020

    • Author(s)
      Kawashima Akihiro、Oba Tomohiro、Yasuhara Rika、Sekiya Bunbu、Sekizawa Akihiko
    • Journal Title

      Prenatal Diagnosis

      Volume: Epub Issue: 6 Pages: 728-737

    • DOI

      10.1002/pd.5679

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PLAG1 enhances the stemness profiles of acinar cells in normal human salivary glands in a cell type-specific manner2020

    • Author(s)
      Goto Yuriko、Ibi Miho、Sato Hirotaka、Tanaka Junichi、Yasuhara Rika、Aota Keiko、Azuma Masayuki、Fukada Toshiyuki、Mishima Kenji、Iri? Tarou
    • Journal Title

      Journal of Oral Biosciences

      Volume: 62 Issue: 1 Pages: 99-106

    • DOI

      10.1016/j.job.2020.01.002

    • NAID

      120006955868

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sox9 regulates the luminal stem/progenitor cell properties of salivary glands2019

    • Author(s)
      Tanaka Junichi、Mabuchi Yo、Hata Kenji、Yasuhara Rika、Takamatsu Koki、Kujiraoka Satoko、Yukimori Akane、Takakura Ikuko、Sumimoto Hidetoshi、Fukada Toshiyuki、Azuma Masayuki、Akiyama Haruhiko、Nishimura Riko、Shimane Toshikazu、Mishima Kenji
    • Journal Title

      Experimental Cell Research

      Volume: 382 Issue: 1 Pages: 111449-111449

    • DOI

      10.1016/j.yexcr.2019.05.030

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Massively parallel sequencing of cell-free DNA in plasma for detecting gynaecological tumour-associated copy number alteration.2018

    • Author(s)
      Nakabayashi M, Kawashima A, Yasuhara R, Hayakawa Y, Miyamoto S, Iizuka C, Sekizawa A.
    • Journal Title

      Sci Rep.

      Volume: 8(1):15883 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41598-018-34168-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of orthotopically functional salivary gland from embryonic stem cells2018

    • Author(s)
      Tanaka Junichi、Ogawa Miho、Hojo Hironori、Kawashima Yusuke、Mabuchi Yo、Hata Kenji、Nakamura Shiro、Yasuhara Rika、Takamatsu Koki、Irie Tarou、Fukada Toshiyuki、Sakai Takayoshi、Inoue Tomio、Nishimura Riko、Ohara Osamu、Saito Ichiro、Ohba Shinsuke、Tsuji Takashi、Mishima Kenji
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 4216-4216

    • DOI

      10.1038/s41467-018-06469-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 唾液腺の再生医学:オルガノイド作製とその再生医療への応用2021

    • Author(s)
      安原理佳
    • Organizer
      第65回日本唾液腺学会学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Identification of salivary gland-derived myoepithelial cells using lineage tracing analysis.2020

    • Author(s)
      Yasuhara Rika, Kang Seya, Yukimori Akane, Tanaka Junichi, Kujiraoka Satoko, Mishima Kenji.
    • Organizer
      第109回日本病理学会オンライン総会
    • Related Report
      2020 Research-status Report
  • [Presentation] Mouse salivary gland-derived myoepithelial cells differentiate into ductal lineage via Notch signaling.2020

    • Author(s)
      Yasuhara Rika, Kang Seya, Yukimori Akane, Tanaka Junichi, Kujiraoka Satoko, Mishima Kenji.
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Loss of ZIP10 impairs skeletal development via osteochondrocyte functions.2019

    • Author(s)
      Rika Yasuhara, Akihiro Kawashima, Akane Yukimori, Junichi Tanaka, Satoko Kujiraoka, Toshiyuki Fukada, Motomi Enomoto-Iwamoto, Kenji Mishima
    • Organizer
      ASBMR 2019 Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The essential role of zinc transporter ZIP10 in skeletal formation2018

    • Author(s)
      Rika Yasuhara, Toshiyuki Fukada, Motomi Enomoto-Iwamoto, Kenji Mishima
    • Organizer
      ANZBMS Annual Scientific Meeting 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 亜鉛トランスポーターの骨格形成における役割の解析2018

    • Author(s)
      安原 理佳,深田 俊幸,岩本 資己 ,美島 健二
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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