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EFFECT OF CASPASE 3 ON BONE METABOLISM

Research Project

Project/Area Number 19592159
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionShowa University

Principal Investigator

AMANO Hitoshi  Showa University, 歯学部, 准教授 (90212571)

Co-Investigator(Kenkyū-buntansha) TANAKA Sakae  東京大学, 医学部, 准教授 (50282661)
TAKAHASHI Katsuhiko  星薬科大, 薬学部, 准教授 (80307066)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2009: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2008: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywordsカスパーゼ3 / 破骨細胞 / アポトーシス / 骨吸収 / 下顎前突症 / カスパーゼ / Caspase3 / 骨 / リモデリング / ミトコンドリア
Research Abstract

Apoptosis is defined as programmed cell death, which is characterized by cell contraction and fragmentation, and nuclear aggregation and fragmentation. Various types of molecular signaling control Apoptosis. Caspase3, a type of cysteine protease, can be activated by stimulus, leading to degradation of a broad range of intracellular substances such as PARP and to induction of apoptosis. Approximately one-half of osteoblasts involved in bone formation undergo apoptosis during the process of transformation into osteocytes when embedded within the bone. In addition, osteoclasts are known to enter apoptosis away from the bone surface after bone resorption. Apoptosis in bone-related cells is considered an essential metabolic system in bone structure ; moreover, Caspase3 may play a significant role in this process. We investigated the role of Caspase3 via utility of mice carrying a Caspase3 gene deficiency. Following completion of visual observation and x-ray photography of mouse skulls (8 we … More eks of age), skullcaps from mice with the gene deficiency exhibited quaquaversal (dome-like) formation characterized by an obtuse angle between the eye-ear plane and the anteroposterior diameter of the occipital skull-base in comparison with the wild type ; consequently, growth suppression of the skull was apparent. Moreover, in mice with the gene deficiency, increased membranous ossification and mandibular prognathism were detected with increasing age. Newborn tibias, following fixation as tissue sections by conventional fixation, were decalcified, embedded in paraffin. Mice with the gene deficiency displayed elevated osteoblast OPG mRNA expression in comparison to the wild type. Increased calcification in osteoblasts carrying the gene deficiency was also demonstrated in vitro. There was no significant difference in osteoclast formation between Caspase 3-/- mice and their littermate. In constrast, caspase3 -/- osteoclast increased bone resorbing activity. This study confirmed abnormal skull formation with increased bone formation and resorption in mice lacking the Caspase3 gene, which controls apoptosis. Caspase3 gene maintains a delicate balance between bone formation and bone resorption ; moreover, it adjusts normal skull development via control of apoptosis in osteoblasts and osteoclasts. Less

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (31 results)

All 2010 2009 2008 2007

All Journal Article (16 results) (of which Peer Reviewed: 14 results) Presentation (15 results)

  • [Journal Article] Diclofenac sodium inhibits NFkappaB transcription in osteoclasts.2009

    • Author(s)
      Karakawa A, Fukawa Y, Okazaki M, Takahashi K, Sano T, Amano H, Yamamoto M, Yamada S.
    • Journal Title

      J Dent Res. 88巻

      Pages: 1042-1047

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts2009

    • Author(s)
      Nagase Y, Iwasawa M, Akiyama T, Kadono Y, Nakamura M, Oshima, Y, Yasui T, Matsumoto T, Hirose J, Nakamura H, Miyamoto T, Bouillet P, Nakamura K, Tanaka S.
    • Journal Title

      J Biol Chem. 284

      Pages: 36659-36669

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diclofenac sodium inhibits NFkappaB transcription in osteoclasts2009

    • Author(s)
      Karakawa A, Fukawa Y, Okazaki M, Takahashi K, Sano T, Amano H, Yamamoto M, Yamada S.
    • Journal Title

      J Dent Res. 88

      Pages: 1042-1047

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [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, Hennighausen L, Nakamura K, Tanaka S., 他5名
    • Journal Title

      J Clin Invest. 119

      Pages: 3149-3159

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tulobuterol promotes osteoclast formation in co-culture system2009

    • Author(s)
      Fukama Y, Usui M, Amano H, Yamamoto M, Yamada S.
    • Journal Title

      Dent Med Res. 29

      Pages: 8-13

    • NAID

      10025646068

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ビスホスホネート系薬剤と顎骨壊死の現状、ならびに薬剤師による情報提供への期待2009

    • Author(s)
      天野均
    • Journal Title

      都薬雑誌 31

      Pages: 5-9

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Brain-type creatine kinase has a crucial role in osteoclast-mediated bone resorption.2008

    • Author(s)
      Chang E-J, Tanaka S, Kim H-H, 他14名.
    • Journal Title

      Nature medicine 14巻

      Pages: 966-972

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pivotal role of Bcl-2 family proteins in the regulation of chondrocyte apoptosis.2008

    • Author(s)
      Oshima Y, Wakeyama H, Tanaka S, et al..
    • Journal Title

      J Biol Chem. 283巻

      Pages: 26499-26508

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-mobility group box proteins modulate tumor necrosis factor-alpha expression in osteoclastogenesis via a novel deoxyribonucleic acid sequence.2008

    • Author(s)
      Yamoah K, Amano H, Abe E, et al.
    • Journal Title

      Mol Endocrinol. 22巻

      Pages: 1141-1153

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] High-mobility group box proteins modulate tumor necrosis factor-alpha expression in osteoclastogenesis via a novel deoxyribonucleic acid sequence.2008

    • Author(s)
      Yamoah K, Amano H, Abe E, et al.
    • Journal Title

      Mol Endocrinol. 22

      Pages: 1141-1153

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin F(2alpha) negatively regulates bone resorption in murine osteoclast development.2008

    • Author(s)
      Kamon M, Fujita D, Goto N, Amano H, Sakamoto K.
    • Journal Title

      Prostaglandins Other Lipid Mediat. 87

      Pages: 26-33

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pivotal role of Bc1-2 family proteins in the regulation of chondrooyte apoptosis.2008

    • Author(s)
      Oshima Y, Wakeyama H, Tanaka s, et al. .
    • Journal Title

      J Biol Chem. 283

      Pages: 26499-26508

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High Mobility Group Box Proteins(HMGBs)Modulate TNF α Expression in Osteoclastogenesis via a Novel DNA Sequence2008

    • Author(s)
      Yamoah K, Amano H, Wang R, Yanagisawa R, Abe E, 他6名
    • Journal Title

      Mol Endocrinol (印刷中)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ビスボスホネート製剤による顎骨壊死の発症機序〜骨代謝学からわかること2008

    • Author(s)
      天野 均、唐川 亜希子
    • Journal Title

      歯界展望 (印刷中)

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Negative feedback loop in the Bim-caspase-3 axis regulating apoptosis and activity of osteoclasts.2007

    • Author(s)
      Wakeyama H, Takahashi K, Amano H, Tanaka S., 他9名
    • Journal Title

      J Bone Miner Res. 22巻

      Pages: 1631-1639

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Negative feedback loop in the Bim-caspase-3 axis regulating apoptosis and activity of osteoclasts2007

    • Author(s)
      Wakeyama H, Takahashi K, Amano H, Tanaka S, 他9名
    • Journal Title

      J Bone Miner Res. 22巻・10号

      Pages: 1631-1639

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] 骨代謝と創薬-アップデート2010

    • Author(s)
      天野均
    • Organizer
      第83回日本薬理学会年会
    • Place of Presentation
      大阪
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report 2009 Final Research Report
  • [Presentation] p57Kip2とビタミンD受容体の蛋白複合体形成による骨代謝への影響2010

    • Author(s)
      天野均, 高橋勝彦, 唐川亜希子, 浦野友彦, 臼井貴彦, 井上聡, 山田庄司
    • Organizer
      昭和大学歯学部ハイテクリサーチ・センター 平成21年度研究成果発表会
    • Place of Presentation
      東京
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] Regulation of Apoptosis and Function of Osteoclasts2009

    • Author(s)
      田中栄
    • Organizer
      The 26th NAITO CONFERENCE
    • Place of Presentation
      兵庫
    • Year and Date
      2009-11-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] Different effects of enantiomer of beta2-Adrenergic on bone resorption2009

    • Author(s)
      Amano H, Fukawa Y, Waki Y, Karakawa A, Usui M, Takeda S, Yamamoto M, Yamada S, Miyamoto K.
    • Organizer
      ASBMR 31st annual Meeting
    • Place of Presentation
      Denver
    • Year and Date
      2009-09-12
    • Related Report
      2009 Annual Research Report
  • [Presentation] Pacemaker channel HCN1 affects osteoclastformation in vitro and bone remodeling in vivo2009

    • Author(s)
      Notomi T, Tanaka S, Amano H, Nakamura T, Noda M, Sherry T, Kuno M.
    • Organizer
      ASBMR 31st annual Meeting
    • Place of Presentation
      Denver
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] 硬組織の石灰化不全層はマグネシウムが増加した後に自己修復される2009

    • Author(s)
      佐野恒吉, 諸橋富夫, 天野均, 山田庄司, 中村雅典
    • Organizer
      第27回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] β2アドレナリン受容体アゴニストの光学異性体による破骨細胞形成能の違いについて2009

    • Author(s)
      天野均, 臼井通彦, 脇能広, 唐川亜希子, 竹田秀, 山本松男, 山田庄司, 宮本謙一
    • Organizer
      第27回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] 窒素含有型ビスフォスフォネートによる破骨細胞アポトーシスと骨吸収能の制御メカニズム2009

    • Author(s)
      田中栄
    • Organizer
      第27回日本骨代謝学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] ペースメーカーチャネル(HCN1)の破骨細胞機能と骨代謝機構への関与2009

    • Author(s)
      納富拓也, 田中伸哉, 天野均, 中村利孝, 野田正樹, 久野みゆき
    • Organizer
      第27回日本骨代謝学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-07-23
    • Related Report
      2009 Annual Research Report
  • [Presentation] Regulation of Bone Destruction in Rheumatoid Arthritis2009

    • Author(s)
      田中栄
    • Organizer
      2009 Annual Symposium in Institute of Rheumatology
    • Place of Presentation
      Seoul
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] Regulation of osteoclast apoptosis and function2009

    • Author(s)
      Tanaka S
    • Organizer
      3rd NEW YORK SKELETAL BIOLOGY AND MEDICINE
    • Place of Presentation
      New York
    • Year and Date
      2009-05-01
    • Related Report
      2009 Final Research Report
  • [Presentation] Regulation of osteoclast apoptosis and function2009

    • Author(s)
      田中栄
    • Organizer
      3rd NEW YORK SKELETAL BIOLOGY AND MEDICINE
    • Place of Presentation
      NEW YORK
    • Year and Date
      2009-05-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] EFFECT OF CASPASE 3 ON BONE METABOLISM2008

    • Author(s)
      Amano H, Karakawa A, Yamada S, et. al.
    • Organizer
      2nd International Conference on Osteoimmunology
    • Place of Presentation
      ギリシャ国ロードス島
    • Year and Date
      2008-06-09
    • Related Report
      2009 Final Research Report
  • [Presentation] EFFECT OF CASPASE 3 0N BONE METABOLISM2008

    • Author(s)
      Amano H, Karakawa A, Yamada S, e
    • Organizer
      2nd International Conference on Osteoimmunology
    • Place of Presentation
      ギリシャ国ロードス島
    • Year and Date
      2008-06-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] 破骨細胞特異的ノックアウトマウスを用いた抗アポトーシス分子Bc1-xLの機能解析2007

    • Author(s)
      岩澤 三康, 田中 栄, 加藤 茂明, ほか10名
    • Organizer
      第25回日本骨代謝学会
    • Place of Presentation
      大阪
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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