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Functional analyses of mutant NLRP3 on the growth and differentiation of growth plate chondrocytes

Research Project

Project/Area Number 15K15549
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionKyoto University

Principal Investigator

Toguchida Junya  京都大学, ウイルス・再生医科学研究所, 教授 (40273502)

Co-Investigator(Kenkyū-buntansha) 池谷 真  京都大学, iPS細胞研究所, 准教授 (20442923)
金 永輝  京都大学, 医学研究科, 特定助教 (90620344)
Co-Investigator(Renkei-kenkyūsha) SHIMAZAKI Takeo  金沢医科大学, 総合医学研究所, 准教授 (50377420)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsCINCA症候群 / NLRP3 / 成長軟骨 / iPS細胞 / 成長板軟骨細胞 / 細胞間相互作用
Outline of Final Research Achievements

CINCA syndrome is one of auto-inflammatory diseases with a heterozygous mutation of NLRP3 gene and characterized as showing joint deformities along with symptoms related to chronic inflammation. To investigate the molecular mechanisms causing the abnormal growth plate, iPS cells with and without mutant NLRP3 gene were established and labeled with different markers, which can distinguish them. Chondrocytes were induced from each type of iPS cells and were cultured under the condition in which they shared culture supernatants. The results indicated that chondrocytes with mutant NLPR3 affected the phenotype of chondrocytes without the mutant gene by producing soluble factors.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (17 results)

All 2016 2015

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 4 results,  Invited: 5 results)

  • [Journal Article] BMP-SMAD-ID promotes reprogramming to pluripotency by inhibiting p16/INK4A-dependent senescence2016

    • Author(s)
      Hayashi, Y., Hsiao, EC., Sami, S., Lancero, M., Schlieve, CR., Nguyen, T., Yano, K., Nagahashi, A., Ikeya, M., Matsumoto, Y., Nishimura, K., Fukuda, A., Hisatake, K., Tomoda, K., Asaka, I., Toguchida, J., Conklin, BR., and Yamanaka, S
    • Journal Title

      Proc. Natl. Acad. Sci. U S A

      Volume: 113 Pages: 13057-13062

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Neofunction of ACVR1 in Fibrodysplasia Ossificance Progressiva2016

    • Author(s)
      Hino K, Ikeya M, Horigome K, Matsumoto Y, Ebise H, Nishio M, Sekiguchi K, Shibata M, Nagata S, Matsuda S, Toguchida J
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 112 Issue: 50 Pages: 15438-15443

    • DOI

      10.1073/pnas.1510540112

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phenotypic differences of patients with fibrodysplasia ossificans progressive due to p.Arg258Ser variants of ACVR12016

    • Author(s)
      Nakahara Y, Suzuki R, Katagiri T, Toguchida J, Haga N
    • Journal Title

      Human Genome Variation

      Volume: 2 Issue: 1 Pages: 15055-15055

    • DOI

      10.1038/hgv.2015.55

    • URL

      https://pure.teikyo.jp/en/publications/6c8a2cb3-428a-4574-8d29-ffa051e686bd

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] New Protocol to Optimize iPS Cells for Genome Analysis of Fibrodysplasia Ossificans Progressiva.2015

    • Author(s)
      Matsumoto Y, Ikeya M, Hino K, Horigome K, Fukuta M, Watanabe M, Nagata S, Yamamoto T, Otsuka T, Toguchida J.
    • Journal Title

      Stem Cells.

      Volume: 印刷中 Issue: 6 Pages: 1730-1742

    • DOI

      10.1002/stem.1981

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] IKKβ in postnatal perichondrium remotely controls endochondral ossification of the growth plate through downregulation of MCP-52015

    • Author(s)
      Kobayashi K, Toguchida J, Karin M, Kato T Jr
    • Journal Title

      Cell Death Differ

      Volume: 22 Issue: 5 Pages: 852-861

    • DOI

      10.1038/cdd.2014.192

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced chondrogenesis of induced pluripotent stem cells from patients with neonatal-onset multisystem inflammatory disease occurs via the caspase 1-independent cAMP/protein kinase A/CREB pathway2015

    • Author(s)
      Yokoyama, K. Ikeya, M. Umeda, K. Oda, H. Nodomi, S. Nasu, A. Matsumoto, Y. Izawa, K. Horigome, K. Kusaka, T. Tanaka, T. Saito, M. K. Yasumi, T. Nishikomori, R. Ohara, O. Nakayama, N. Nakahata, T. Heike, T. Toguchida, J.
    • Journal Title

      Arthritis Rheumatol

      Volume: 67 Issue: 1 Pages: 302-314

    • DOI

      10.1002/art.38912

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] iPS細胞由来軟骨細胞とバイオ3Dプリンタを用いた立体的軟骨構造体の作製2016

    • Author(s)
      田中麻衣、薦田博、長池碧、永田早苗、戸口田淳也、中山功一
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] 疾患特異的iPS細胞を活用した骨格疾患の病態解明2016

    • Author(s)
      戸口田淳也、日野恭介、池谷真、関口和也、金永輝、岡本健、吉富啓之、松田秀一
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Investigation of molecular mechanism underlying enhanced chondrogenesis in neonatal-onset multisystem inflammatory disease using patient-derived induced pluripotent stem cells.2016

    • Author(s)
      Tamaki, S., Watanabe, M., Yamamoto, R., Yoshitomi, H., Nishikomori, R., and Toguchida, J.
    • Organizer
      ISSCR 2016 Annual Meeting
    • Place of Presentation
      San Francisco(USA)
    • Year and Date
      2016-06-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 疾患特異的iPS細胞を用いた創薬に向けた薬剤スクリーニング系の構築2016

    • Author(s)
      松本佳久、池谷真、日野恭介、福田誠、大塚隆信、戸口田淳也
    • Organizer
      第89回日本整形外科学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] 疾患特異的iPS細胞を用いた成長軟骨病態解析2015

    • Author(s)
      玉置さくら、渡辺真、梅田雄嗣、西小森隆太、戸口田淳也
    • Organizer
      第27回日本整形外科学会骨系統疾患研究会
    • Place of Presentation
      長良川国際会議場(岐阜県岐阜市)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 疾患特異的iPS細胞を活用した希少難病の病態解明から創薬2015

    • Author(s)
      戸口田淳也
    • Organizer
      日本人類遺伝学第60回大会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 疾患特異的iPS細胞を用いたCINCA症候群における成長軟骨病態の解析.2015

    • Author(s)
      戸口田淳也、横山宏司、玉置さくら、池谷真、田中孝之、斉藤潤、梅田雄嗣、中畑龍峻、平家俊男、西小森隆太
    • Organizer
      第1回骨免疫学会
    • Place of Presentation
      ホテルブリーズベイマリーナ宮古島(沖縄県宮古島市)
    • Year and Date
      2015-07-01
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enhanced chondrogenesis of induced pluripotent stem cells from patients with neonatal-onset multisystem inflammatory disease occurs via the caspase 1-independent cAMP/PKA/CREB pathway2015

    • Author(s)
      Toguchida J, Yokoyama K, Umeda K, Saito KM, Ikeya M, Nakahata T, Heike T, Nishikomori R
    • Organizer
      第13回ISSCR
    • Place of Presentation
      Stockholm(Sweden)
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨軟骨領域におけるiPS細胞研究.2015

    • Author(s)
      戸口田淳也
    • Organizer
      第35回日本骨形態計測学会学術集会
    • Place of Presentation
      倉敷市芸文館(岡山県倉敷市)
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Application of the iPS cell technology for musculoskeletal diseases2015

    • Author(s)
      Toguchida J
    • Organizer
      第15回International Congress of Radiation Research
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-05-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 疾患特異的iPS細胞を活用した難治性骨軟骨疾患の病態解明2015

    • Author(s)
      戸口田淳也、松本佳久、横山宏司、松田秀一、西小森隆太、池谷真
    • Organizer
      第88回日本整形外科学会学術総会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
    • Invited

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Published: 2015-04-16   Modified: 2018-03-22  

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