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2011 Fiscal Year Final Research Report

Molecul ar epidemiological study of the regulation of bone and joint destruction through intracellular ATP and ROS levels

Research Project

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Project/Area Number 21591965
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
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 Yoshinari  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)
TANAKA Sakae  東京大学, 医学部・附属病院整形外科, 教授 (50282661)
Project Period (FY) 2009 – 2011
Keywords骨関節破壊 / 破骨細胞
Research Abstract

Osteoclasts have two conflicting tendencies : lower capacity to survive and higher capacity to execute energy-consuming activities like bone resorption. Here, we report that mature mitochondria-rich osteoclasts have lower intracellular ATP compared to their precursors. Severe ATP depletion caused by disrupting the gene of mitochondrial transcription factor A(Tfam) leads to increased bone-resorbing activity despite accelerated apoptosis. The release of ATP from intracellular stores negatively regulates bone-resorbing activity through an autocrine/paracrine feedback loop by altering cytoskeletal structures. Thus, our study provides evidence for a mechanism by reciprocal changes in intracellular and extracellular ATP, which regulate the negative correlation between osteoclast survival and bone resorption.

  • Research Products

    (25 results)

All 2012 2011 2010 2009

All Journal Article (9 results) (of which Peer Reviewed: 8 results) Presentation (16 results)

  • [Journal Article] 3, 4-Diaminopyridine improvesneuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis2012

    • Author(s)
      Mori S, Kishi M, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Konishi T, Maruyama N, Shigemoto K
    • Journal Title

      J Neuroimmunol

      Volume: 245(1-2) Pages: 75-8

    • DOI

      DOI:10.1016/j.jneuroim.2012.02.010

    • Peer Reviewed
  • [Journal Article] Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis2012

    • Author(s)
      Mori S, Kubo S, Akiyoshi T, Yamada S, Miyazaki T, Hotta H, Desaki J, Kishi M, Konishi T, Nishino Y, Miyazawa A, Maruyama N, Shigemoto K
    • Journal Title

      Am J Pathol

      Volume: 180(2) Pages: 798-810

    • DOI

      DOI:10.1016/j.ajpath.2011.10.031.ISSN:0002-9440.

    • Peer Reviewed
  • [Journal Article] Owing to Low-Turnover Osteoporosis and Impaired CollagenCross-Linking2011

    • Author(s)
      Hidetoshi Nojiri, Yoshitomo Saita, Daichi Morikawa, Keiji Kobayashi, Chizuru Tsuda, Tsuyoshi Miyazaki, Mitsuru Saito, Keishi Marumo, Ikuho Yonezawa, Kazuo Kaneko, Takuji Shirasawa, and Takahiko Shimizu
    • Journal Title

      J Bone Miner Res

      Volume: 26(11) Pages: 2682-94

    • DOI

      DOI:10.1002/jbmr.489.

    • Peer Reviewed
  • [Journal Article] Neutrophil CD64 expression as a diagnostic marker for local infection and crystal-induced arthritis2010

    • Author(s)
      Toru Doi, Tsuyoshi Miyazaki, Jinju Nishino, Sakae Tanaka, Toshihiro Matsui, Akiko Komiya, Seizo Yamamoto, Fumiaki Tokimura, Toshihito Mori, Keita Nishimura, Narutaka Katoh, Jun Hasegawa, Yasunori Omata, Takashi Matsushita, Shigeto Tohma
    • Journal Title

      Mod Rheumatol

      Volume: 20(6) Pages: 573-9

    • DOI

      DOI:10.1007/s10165-010-0322-6

    • Peer Reviewed
  • [Journal Article] Regulation of apoptosis and activity of the osteoclast2010

    • Author(s)
      Tsuyoshi Miyazaki and Sakae Tanaka
    • Journal Title

      Immun., Endoc. & Metab. Agents in Med. Chem

      Volume: 10(2) Pages: 100-107

    • URL

      http://dx.doi.org/10.2174/187152210793176974

    • Peer Reviewed
  • [Journal Article] Muscle weakness and neuromuscular junctions in aging and disease2010

    • Author(s)
      Shigemoto K, Kubo S, Mori S, Yamada S, Akiyoshi T and Miyazaki T
    • Journal Title

      Geriatr Gerontol Int

      Volume: 10 Pages: 137-147

    • DOI

      DOI:10.1111/j.1447-0594.2010.00608.x

  • [Journal Article] The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing activity of osteoclasts in mice2009

    • Author(s)
      Iwasawa M, Miyazaki T, Nagase Y, Akiyama T, Kadono Y, Nakamura M, Oshima Y, Yasui T, Matsumoto T, Nakamura T, Kato S, Hennighausen L, Nakamura K, Tanaka S
    • Journal Title

      J Clin Invest

      Volume: 119(10) Pages: 3149-59

    • DOI

      DOI:10.1172/JCI39819

    • Peer Reviewed
  • [Journal Article] Hiroshi Takayanagi, Kozo Nakamura : Rheumatoid Arthritis associated with osteopetrosis2009

    • Author(s)
      Yuho Kadono, Sakae Tanaka, Jinju Nishino, Keita Nishimura, Ichiro Nakamura, Tsuyoshi Miyazaki
    • Journal Title

      Mod Rheumatol

      Volume: 19(6) Pages: 687-90

    • DOI

      DOI:10.1007/s10165-009-0208-7

    • Peer Reviewed
  • [Journal Article] The Immunopathogenesis of Experimental Autoimmune Myasthenia Gravis induced by Autoantibodies against Muscle-specific kinase2009

    • Author(s)
      Shigemoto K, Kubo S, Mori S, Yamada S, Miyazaki T, Akiyoshi T, Maruyama N
    • Journal Title

      Myasthenia Gravis

      Pages: 305-324

    • DOI

      DOI:10.1196/annals.1405.002

    • Peer Reviewed
  • [Presentation] Bcl-xL regulates osteoclastic bone resorption via extracellular matrix component protein2012

    • Author(s)
      宮崎剛
    • Organizer
      第4回Bone Research Seminar
    • Place of Presentation
      東京
    • Year and Date
      20120219-20
  • [Presentation] Maintenance of mitochondrial DNA copy number is essential for osteoclast survival and 1st bone resorption2011

    • Author(s)
      Tsuyoshi Miyazaki, Shuuichi Mori, Kazuhiro Shigemoto, Nils-Goran Larsson, Takeshi Nakamura, Shigekaki Kato, Tomoki Nakashima, Hiroshi Takayanagi, Sakae Tanaka
    • Organizer
      1st bone resorption. Bio-Rheumatology 8th Internationla Congress Tokyo GARN meeting Tokyo
    • Place of Presentation
      Maihama
    • Year and Date
      20111114-16
  • [Presentation] Distinct mechanisms between divalent and monovalent MuSK antibodies involved with dysfunction of MuSK leading to myasthenia gravis2011

    • Author(s)
      Mori S, Kubo S, Yamada S, Miyazaki T, Shigemoto K
    • Organizer
      Society for Neuroscience
    • Place of Presentation
      Washington, D. C. USA
    • Year and Date
      20111113-18
  • [Presentation] スーパーオキサイドディスムターゼ1(SOD1)による骨代謝制御機構の解析2011

    • Author(s)
      斎田良知、野尻英俊、森川大智、宮崎剛、麻生義則、金子和夫、清水孝彦
    • Organizer
      第26回日本整形外科学会基礎学術集会
    • Place of Presentation
      大阪
    • Year and Date
      20110728-30
  • [Presentation] 破骨細胞特異的ノックアウトマウスによる抗アポトーシス分子Bcl-xLの機能解析ーBcl-xLは破骨細胞の骨吸収に抑制的に働くー2011

    • Author(s)
      岩澤三康、永瀬雄一、宮崎剛、中村耕三、田中栄
    • Organizer
      第84回日本整形外科学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      20110512-15
  • [Presentation] 細胞質酸化ストレスの増加は骨量および骨質の低下を引き起こす2011

    • Author(s)
      森川大智、野尻英俊、斎田良和、小林慶司、宮崎剛、齋藤充、丸毛啓史、金子和夫、清水孝彦
    • Organizer
      第84回日本整形外科学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      20110512-15
  • [Presentation] Distinct mechanisms between divalent and monovalent MuSK antibodiesinvolved with dysfunction of MuSK leading to myasthenia gravis2011

    • Author(s)
      Mori S, Kubo S, Yamada S, Miyazaki T, Shigemoto K
    • Organizer
      34回日本神経科学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2011-09-15
  • [Presentation] Intracellular superoxide dismutase deficiency decreased bone mass in vivo by impairment of cell viability and redox balance in osteoblasts2010

    • Author(s)
      Yoshitomo Saita, Hidetoshi Nojiri, Chizuru Tsuda, Tsuyoshi Miyazaki, Daichi Morikawa, Kazuo Kaneko, Takahiko Shimizu
    • Organizer
      Thirty-second Annual Meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Toronto, Canada
    • Year and Date
      20101015-19
  • [Presentation] 筋は逆行性シグナルにより筋・運動神経を維持する2010

    • Author(s)
      森秀一、久保幸穂、秋好沢論、山田茂、宮崎剛、重本和宏
    • Organizer
      日本基礎老化学会大33回大会
    • Place of Presentation
      名古屋
    • Year and Date
      20100617-18
  • [Presentation] Mouse lacking in intracellular superoxide dismutase increased reactive oxygen spices in osteoblasts and suppressed osteoblastic ability leading to osteoporotic phenotypes in bone. IOF World Congress on Osteoporosis2010

    • Author(s)
      Yoshitomo Saita, Hidetoshi Nojiri, Chizuru Tsuda, Tsuyoshi Miyazaki, Daichi Morikawa, Kazuo Kaneko, Takahiko Shimizu
    • Organizer
      10th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis
    • Place of Presentation
      Italy
    • Year and Date
      20100505-08
  • [Presentation] Anti-apoptotic Molecule Bcl-xL regulates osteoclastic bone resorption via extracellular matrix component expression2009

    • Author(s)
      Tsuyoshi Miyazaki, Mitsuyasu Iwasawa, Yuichi Nagase, Yuho Kadono, Lothar Henninghausen, Takashi Nakamura, Shigeaki Kato, Kozo Nakamura, Sakae Tanaka
    • Organizer
      The 26th NAITO Conference on Osteobioloty Awaji Yumebutai
    • Place of Presentation
      Hyogo, Japan
    • Year and Date
      20091104-07
  • [Presentation] MuSKは神経筋シナプスの維持に重要であるー研究モデル動物の確立2009

    • Author(s)
      森秀一、久保幸穂、秋吉沢諭、山田茂、宮崎剛、重本和宏
    • Organizer
      日本基礎老化学会第32回大会
    • Place of Presentation
      横浜
    • Year and Date
      20090618-20
  • [Presentation] 結晶性関節炎と感染性関節炎の鑑別における好中球CD64値の有用性2009

    • Author(s)
      滝田泰人、西野仁寿、濱路博、宮崎剛、松井利浩、小宮明子、田中栄、時村文秋、當間重人
    • Organizer
      第82回日本整形外科学会学術総会
    • Place of Presentation
      博多
    • Year and Date
      20090514-17
  • [Presentation] 高齢者TKAにおけるmini-mental state examinationを用いた術前認知機能評価の有用性2009

    • Author(s)
      宮本恵成、濱路博、宮崎剛、穴水依人、時村文秋、石橋英明、山本精三
    • Organizer
      第82回日本整形外科学会学術総会
    • Place of Presentation
      博多
    • Year and Date
      20090514-17
  • [Presentation] 骨関節感染症における好中球上CD64分子発現の発現計測の有用性-第二報告-2009

    • Author(s)
      西野仁寿、松井利浩、小宮明子、田中栄、門野夕峰、中村正樹、宮崎剛、當間重人
    • Organizer
      第53回日本リウマチ学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      20090423-25
  • [Presentation] 関節リウマチにおける結晶アルギニンデイミナーゼ4(PAD4)及び抗PAD4抗体の検討2009

    • Author(s)
      木村直樹、宮崎剛、杉原毅彦
    • Organizer
      第53回日本リウマチ学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      20090423-25

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Published: 2013-07-31  

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