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Mechanosensor protein p130Cas in osteocytes is important for bone metabolism

Research Project

Project/Area Number 24592290
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionTokyo Metropolitan Geriatric Hospital and Institute of Gerontology

Principal Investigator

MIYAZAKI TSUYOSHI  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (50376480)

Co-Investigator(Kenkyū-buntansha) MIYAMOTO Yoshinaro  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (10345217)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsメカニカルストレス / 骨細胞 / p130Cas
Outline of Final Research Achievements

The adaptor molecule p130Cas, which is phosphorylated at focal adhesions upon extracellular matrix engagement, is involved in various cellular processes including migration, survival, transformation, and invasion.
To investigate the role of Cas in bone metabolism, we generated osteocyte-specific Cas conditional knockout (cKO) mice by mating Casflox/flox mice with Dmp1-Cre transgenic mice, in which the Cre recombinase gene was specifically expressed in osteocytes. The resulting Cas cKO mice exhibited a remarkable decrease in bone volume. Histomorphometric analysis of Cas cKO mice revealed a significant increase in the eroded surface/bone surface ratio, osteoclast surface, and osteoclast number. However, the bone formation parameters were equivalent to those in normal Casflox/flox littermates. Collectively, these findings suggest that the bone loss in Cas cKO mice was caused by increased bone-resorbing activity, rather than by decreased bone formation.

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

All Journal Article (11 results) (of which Peer Reviewed: 5 results) Presentation (6 results)

  • [Journal Article] Quantitative SHG imaging in osteoarthritis model mice, implying a diagnostic application2015

    • Author(s)
      Hiroshi Kiyomatsu, Yusuke Oshima, Takashi Saitou, Tsuyoshi Miyazaki, Atsuhiko Hikita, Hiromasa Miura, Tadahiro Iimura, and Takeshi Imamura
    • Journal Title

      Biomedical Optics Express.

      Volume: 6 Pages: 405-20

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A review of denosumab for the treatment of osteoporosis.2014

    • Author(s)
      Miyazaki T, Tokimura F, Tanaka S
    • Journal Title

      Patient Prefer Adherence.

      Volume: 8 Pages: 463-471

    • DOI

      10.2147/ppa.s46192

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 骨代謝を制御する「善玉」メカニカルストレスと「悪玉」メカニカルストレス2014

    • Author(s)
      澤田泰宏、宮崎剛、原田伊知郎
    • Journal Title

      実験医学

      Volume: 32 Pages: 1093-1099

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Anti-apoptotic Bcl-2 family member Mcl-1 regulates cell viability and bone-resorbing activity of osteoclasts2014

    • Author(s)
      Masuda H, Hirose J, Omata Y, Tokuyama N, Yasui T, Kadono Y, Miyazaki T, Tanaka S
    • Journal Title

      Bone

      Volume: 58 Pages: 1

    • DOI

      10.1016/j.bone.2013.09.020

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Two novel sandwich ELISAs identify PAD4 levels and PAD4 autoantibodies in patients with rheumatoid arthritis.2013

    • Author(s)
      2) Ishigami A, Uchida Y, Miyazaki T, Handa S, Choi EK, Kim YS, Kasahara Y, Maruyama N
    • Journal Title

      Mod Rheumatol

      Volume: 23 Pages: 794-803

    • NAID

      10031189176

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] ミトコンドリアによる破骨細胞機能制御2013

    • Author(s)
      宮崎剛
    • Journal Title

      Clin Calcium

      Volume: 23 Pages: 1577-83

    • Related Report
      2013 Research-status Report
  • [Journal Article] 骨粗鬆症研究と治療法の進歩2013

    • Author(s)
      宮崎剛、澤田泰宏
    • Journal Title

      日本老年医学会雑誌

      Volume: 50 Pages: 130-134

    • Related Report
      2013 Research-status Report 2012 Research-status Report
  • [Journal Article] サルコペニア発症のメカニズム2013

    • Author(s)
      4) 宮崎剛、森秀一、重本和宏
    • Journal Title

      腎と骨代謝

      Volume: 26 Pages: 99-107

    • Related Report
      2013 Research-status Report
  • [Journal Article] Intracellular and extracellular ATP coordinately regulate the inverse correlation between osteoclast survival and bone resorption.2012

    • Author(s)
      Miyazaki T, Iwasawa M
    • Journal Title

      J Biol Chem.

      Volume: 287(45) Issue: 45 Pages: 34808-23

    • DOI

      10.1074/jbc.m112.385369

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] サルコペニア発症のメカニズム2012

    • Author(s)
      宮崎剛、森秀一、重本和宏
    • Journal Title

      腎と骨代謝

      Volume: 26 Pages: 99-107

    • Related Report
      2012 Research-status Report
  • [Journal Article] 老齢マウスの筋繊維タイプ特異的な筋萎縮の病態解明2012

    • Author(s)
      福永大地、久保幸穂、森秀一、宮崎剛、樋上賀一、重本和宏
    • Journal Title

      基礎老化研究

      Volume: 36 Pages: 47-49

    • Related Report
      2012 Research-status Report
  • [Presentation] MECHANOSENSOR PROTEIN P130CAS IN OSTEOCYTES IS IMPORTANT FOR BONE METABOLISM.2015

    • Author(s)
      Miyazaki T, Harada I, Sawada Y.
    • Organizer
      The 2015 Ageing Summit.
    • Place of Presentation
      London
    • Year and Date
      2015-02-11 – 2015-02-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Evaluation of cartilage based on second harmonic generation microscopy2014

    • Author(s)
      Hiroshi Kiyomatsu, Takeshi Imamura, Atsuhiko Hikita, Tadahiro Iimura, Tsuyoshi Miyazaki, Yusuke Ohsima, Takashi Saitou, Hiromasa Miura
    • Organizer
      Thirty-sixth Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Houston, Texas, USA.
    • Year and Date
      2014-09-12 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] A novel murine model of myasthenia gravis with MuSK antibodies.2012

    • Author(s)
      Mori, S., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Hotta, H., Desaki, J., Kishi, M., Konishi, T., Maruyama, N. and Shigemoto, K
    • Organizer
      12th International conference on myasthenia gravis and related disorders
    • Place of Presentation
      New York
    • Related Report
      2012 Research-status Report
  • [Presentation] Examination of the treatment of myasthenia gravis with anti-MuSK antibodies using an experimental autoimmune animal model. 12th International conference on myasthenia gravis and related disorders2012

    • Author(s)
      Mori, S., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Hotta, H., Desaki, J., Kishi, M., Konishi, T., Maruyama, N. and Shigemoto, K.
    • Organizer
      12th International conference on myasthenia gravis and related disorders
    • Place of Presentation
      New York
    • Related Report
      2012 Research-status Report
  • [Presentation] Effectiveness of 3,4-diaminopyridine to symptomatic treatment of a MuSK antibody-induced mouse model of myasthenia gravis2012

    • Author(s)
      Mori, S., Kubo, S., Akiyoshi, T., Yamada, S., Miyazaki, T., Kishi, M. and Shigemoto, K.
    • Organizer
      第35回日本神経科学大会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Research-status Report
  • [Presentation] Muscle fiber type specific pathology in aging mouse.2012

    • Author(s)
      Fukunaga, T., Kubo, S., Mori, S., Miyazaki, T., Higami, Y. and Shigemoto, K.
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report

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

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