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Elucidation of the role of Sirt6 in the chondrocyte metabolism

Research Project

Project/Area Number 24592257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

ASOU Yoshinori  東京医科歯科大学, 医歯(薬)学総合研究科, 准教授 (50345279)

Co-Investigator(Kenkyū-buntansha) 辻 邦和  東京医科歯科大学, 大学院医歯(薬)学総合研究科, 准教授 (20323694)
荻島 創一  東北大学, 学内共同利用施設等, 准教授 (40447496)
Co-Investigator(Renkei-kenkyūsha) 荻島 創一  東北大学, 東北メディカルメガバンク機構, 講師 (40447496)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsサーチュイン / 軟骨代謝 / 老化 / 加齢 / 骨代謝 / Sirt6
Outline of Final Research Achievements

The aim of this study was to investigate the Sirt6 signal pathway in cartilage metabolism.Sirt6 was expressed in primary chondrocytes and the chondrocyte-like cell line ATDC5. At birth, the length of the tibia and femur was shorter in Sirt6-/-. In the growth plate (GP), PCNA expression was reduced in Sirt6-/- mice. The number of TUNEL positive cells was comparable between Sirt6-/- and littermates. Two weeks after birth, growth retardation was apparent in Sirt6-/-, with reduced proliferating zone and hypertrophic zone in the growth plate, delayed ossification of secondary ossification center and decreased primary spongiosa. mRNA and protein expression of Col2a1, Col10a1 and Ihh in the growth plate was reduced in Sirt6-/- primary chondrocytes. Functional analysis revealed Sirt6 positively regulates chondrocyte differentiation via the Atf4 -Ihh axis.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (17 results)

All 2015 2014 2013 2012 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 1 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Enhancement of Runx2 expression is potentially linked to β-catenin accumulation in canine intervertebral disc degeneration.2015

    • Author(s)
      Iwata M, Aikawa T, Hakozaki T, Arai K, Ochi H, Haro H, Tagawa M, Asou Y, Hara Y.
    • Journal Title

      J Cell Physiol.

      Volume: Jan;230(1) Issue: 1 Pages: 180-190

    • DOI

      10.1002/jcp.24697

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial superoxide in osteocytes perturbs canalicular networks in the setting of age-related osteoporosis.2015

    • Author(s)
      Kobayashi K1, Nojiri H2, Saita Y2, Morikawa D1, Ozawa Y3, Watanabe K3, Koike M1, Asou Y4, Shirasawa T5, Yokote K6, Kaneko K2, Shimizu T3.
    • Journal Title

      Scientific Reports

      Volume: Mar 16;5 Issue: 1 Pages: 9148-9148

    • DOI

      10.1038/srep09148

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Tumor necrosis factor-α enhances RANKL expression in gingival epithelial cells via protein kinase A signaling.2014

    • Author(s)
      Fujihara R, Usui M, Yamamoto G, Nishii K, Tsukamoto Y, Okamatsu Y, Sato T, Asou Y, Nakashima K, Yamamoto M.
    • Journal Title

      J Periodontal Res.

      Volume: Aug;49(4) Issue: 4 Pages: 503-507

    • DOI

      10.1111/jre.12131

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling.2013

    • Author(s)
      Piao J, Tsuji K, Ochi H, Iwata M, Koga D, Okawa A, Morita S, Takeda S, Asou Y.
    • Journal Title

      Scientific Report

      Volume: october 23 Issue: 1 Pages: 3022-3022

    • DOI

      10.1038/srep03022

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cytoplasmic reactive oxygen species and SOD1 regulate bone mass during mechanical unloading.2013

    • Author(s)
      Morikawa D, Nojiri H, Saita Y, Kobayashi K, Watanabe K, Ozawa Y, Koike M, Asou Y, Takaku T, Kaneko K, Shimizu T.
    • Journal Title

      J Bone Miner Res

      Volume: november 28(11) Issue: 11 Pages: 2368-80

    • DOI

      10.1002/jbmr.1981

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Variations in gene and protein expression in canine chondrodystrophic nucleus pulposus cells following long-term three-dimensional culture.2013

    • Author(s)
      Iwata M, Ochi H, Asou Y, Haro H, Aikawa T, Harada Y, Nezu Y, Yogo T, Tagawa M, Hara Y.
    • Journal Title

      PLoS One

      Volume: May 2;8(5)

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sema3A regulates bone-mass accrual through sensory innervations2013

    • Author(s)
      Fukuda T, Takeda S, Xu R, Ochi H, Sunamura S, Sato T, Shibata S, Yoshida Y, Gu Z, Kimura A, Ma C, Xu C, Bando W, Fujita K, Shinomiya K, Hirai T, Asou Y, Enomoto M, Okano H, Okawa A, Itoh H
    • Journal Title

      Nature.

      Volume: 497 Issue: 7450 Pages: 490-493

    • DOI

      10.1038/nature12115

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of the association between runt-related transcription factor 2 expression and intervertebral disk aging in dogs.2012

    • Author(s)
      Itoh H, Hara Y, Tagawa M, Kato T, Ochi H, Koga D, Okawa A, Asou Y.
    • Journal Title

      Am J Vet Res

      Volume: Oct;73(10):1553-9. Pages: 1553-9

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Runx2 haploinsufficiency ameliorates the development of ossification of the posterior longitudinal ligament.2012

    • Author(s)
      Iwasaki M, Piao J, Kimura A, Sato S, Inose H, Ochi H, Asou Y, Shinomiya K, Okawa A, Takeda S.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 8 Pages: e43372-e43372

    • DOI

      10.1371/journal.pone.0043372

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Procyanidin B3 prevents articular cartilage degeneration and heterotopic cartilage formation in a mouse surgical osteoarthritis model.2012

    • Author(s)
      Aini H, Ochi H, Iwata M, Okawa A, Koga D, Okazaki M, Sano A, Asou Y.
    • Journal Title

      PLoS One

      Volume: 7(5) Issue: 5 Pages: e37728-e37728

    • DOI

      10.1371/journal.pone.0037728

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] サーチュイン遺伝子Sirt6による軟骨代謝制御機構の解析2014

    • Author(s)
      朴金瑛1 辻邦和2 越智広樹3 古賀大介1 大川淳1 竹田秀3 麻生義則1
    • Organizer
      日本整形外科学会基礎学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 高脂肪食負荷による膝蓋下脂肪体肥大化は力学的負荷とは独立して変形性膝関節症を惹起する。2014

    • Author(s)
      岩田宗峻1 越智広樹2 原康1 多川政弘1 古賀大介3 大川淳3 麻生義則3
    • Organizer
      日本整形外科学会基礎学会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] サーチュイン遺伝子Sirt6による軟骨代謝制御2012

    • Author(s)
      朴金瑛 辻邦和 越智広樹 森田定雄 古賀大介 大川淳 竹田秀 麻生義則
    • Organizer
      日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] 短期高脂肪食負荷に対するマウス膝関節の初期組織学的反応2012

    • Author(s)
      Munetaka Iwata, Hiroki Ochi, Yasushi Hara, Daisuke Koga, Masahiro Tagawa, Atsushi Okawa, Yoshinori Asou
    • Organizer
      日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] サーチュイン遺伝子Sirt6による軟骨代謝制御2012

    • Author(s)
      麻生 義則
    • Organizer
      東京医科歯科大学第4回硬組織疾患ゲノムセンターセミナー
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Sirt6 regulate proliferation and differentiation of the postnatal growth plate chondrocyte via Ihh signaling.

    • Author(s)
      Jinying Piao1, Kunikazu Tsuji2, Hiroki Ochi3, Sadao Morita1, Daisuke Koga4, Atsushi Okawa4, Shu Takeda5, Yoshinori Asou4
    • Organizer
      Annual meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Baltimore USA
    • Related Report
      2013 Research-status Report
  • [Presentation] The distinct role of the infrapatellar fat pad in a murine high-fat diet-induced osteoarthritis model.

    • Author(s)
      Munetaka Iwata1, Hiroki Ochi2, Yasushi Hara1, Masahiro Tagawa1, Daisuke Koga3, Atsushi Okawa3, Yoshinori Asou3
    • Organizer
      Annual meeting of American Society for Bone and Mineral Research
    • Place of Presentation
      Baltimore USA
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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