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Molecular epidemiological study of the regulation of osteoclastic bone resorption

Research Project

Project/Area Number 19591773
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionTokyo Metropolitan Institute of Gerontology

Principal Investigator

MIYAZAKI Tsuyoshi  Tokyo Metropolitan Institute of Gerontology, 東京都老人総合研究所, 研究員 (50376480)

Co-Investigator(Kenkyū-buntansha) SUZUKI Takao  財団法人東京都高齢者研究・福祉財団, 東京都老人総合研究所, 副所長 (30154545)
TANAKA Sakae  東京大学, 医学部附属病院・整形外科, 准教授 (50282661)
Co-Investigator(Renkei-kenkyūsha) TANAKA Sakae  東京大学, 医学部附属病院・整形外科, 准教授 (50282661)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords破骨細胞 / 骨破壊 / 関節リウマチ / ミトコンドリア / スーパーオキシドディスムターゼ / 骨吸収
Research Abstract

骨粗鬆症や関節リウマチにおける骨量低下・骨破壊の進展においては、骨吸収を直接担う唯一の細胞と考えられている破骨細胞が重要な役割を果たしている。今回、破骨細胞の骨吸収亢進が引き起こされる環境下において、発現量が変化する遺伝子を網羅的に検索したところ、興味深いことに加齢変化において重要といわれている活性酸素を制御する遺伝子MnSOD(スーパーオキシドディスムターゼ)が同定された。MnSOD遺伝子をCre/loxPシステムでノックダウンすると成熟破骨細胞の骨吸収活性が有意に低下することを見いだした。今後、破骨細胞特異的MnSODノックアウトマウスを作製し、解析を行う予定である。

Report

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

    (47 results)

All 2008 2007

All Journal Article (23 results) (of which Peer Reviewed: 23 results) Presentation (15 results) Book (9 results)

  • [Journal Article] MKK6-p38 MAPK signaling pathway enhances survival but not bone-resorbing activity of osteoclasts.2008

    • Author(s)
      Yamashita T, Kobayashi Y, Mizoguchi T, Yamaki M, Miura T, Tanaka S, Udagawa N, Takahashi N.
    • Journal Title

      Biochem Biophys Res Commun. 365

      Pages: 252-257

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Osteoporotic bone formation in mice lacking tob2 ; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation.2008

    • Author(s)
      Ajima R, Akiyama T, Usui M, Yoneda M, Yoshida Y, Nakamura T, Minowa O, Noda M, Tanaka S, Noda T, Yamamoto T.
    • Journal Title

      FEBS Lett. 582

      Pages: 1313-1318

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tumor necrosis factor-alpha inhibits chondrogenic differentiation of synovial fibroblasts through p38 mitogen activating protein kinase pathways.2008

    • Author(s)
      Okuma-Yoshioka C, Seto H, Kadono Y, Hikita A, Oshima Y, Kurosawa H, Nakamura K, Tanaka S.
    • Journal Title

      Mod Rheumatol. 18(4)

      Pages: 366-378

    • Related Report
      2008 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, Akiyama T, Hikita A, Iwasawa M, Nagase Y, Nakamura M, Wakeyama H, Kawamura N, Ikeda T, Chung UI, Hennighausen L, Kawaguchi H, Nakamura K, Tanaka S.
    • Journal Title

      J Biol Chem. 283(39)

      Pages: 26499-26508

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Brain-type creatine kinase has a crucial role in osteoclastmediated bone resorption.2008

    • Author(s)
      Eun-Ju Chang, Jeongim Ha, Frank Oerlemans, You Jin Lee, Soo Woong Lee, Jiyoon Ryu, Hyung Joon Kim, Youngkyun Lee, Hyun-Man Kim, Je- Yong Choi, Jin Young Kim, Chan Soo Shin, Youngmi Kim Pak, Sakae Tanaka, Be Wieringa, Zang Hee Lee, Hong-Hee Kim.
    • Journal Title

      Nature medicine 14

      Pages: 966-972

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potential involvement of p53 in ischemia/reperfusion-induced osteonecrosis.2008

    • Author(s)
      Okuma C, Kaketa T, Hikita A, Matsuda K, Nakamura M, Nagase Y, Oshima Y, Iwasawa M, Nakamura Y, Kurosawa H, Nakamura K, Tanaka S.
    • Journal Title

      J Bone Miner Metab. 26

      Pages: 576-585

    • NAID

      10024460040

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Personality and participation in mass health checkups among Japanese community-dwelling elderly2008

    • Author(s)
      Iwasa H, Masui Y, Gondo Y, Yoshida Y, Inagaki H, Kawaai C, Kim H, Yoshida H, Suzuki T. Iwasa H, Masui Y, Gondo Y, Yoshida Y, Inagaki H, Kawaai C, Kim H, Yoshida H, Suzuki T.
    • Journal Title

      J Psychosom Res. 66

      Pages: 155-159

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The association between self-rated health status and increasing age among older Japanese living in a rural community over a 6-year period : a longitudinal data analysis2008

    • Author(s)
      Ishizaki T, Yoshida H, Suzuki T, Shibata H
    • Journal Title

      Gerontology 55

      Pages: 344-52

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Personality and all-cause mortality among older adults dwelling in a Japanese community : a five-year population-based prospective cohort study2008

    • Author(s)
      Iwasa H, Masui Y, Gondo Y, Inagaki H, Kawaai C, Suzuki T
    • Journal Title

      Am J Geriatr Psychiatry 16

      Pages: 399-405

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low serum 25-hydroxyvitamin D levels associated with falls among Japanese community-dwelling elderly2008

    • Author(s)
      Suzuki T, Kwon J, Kim H, Shimada H, Yoshida Y, Iwasa H, Yoshida H.
    • Journal Title

      J Bone Miner Res 23

      Pages: 1309-1317

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The molecular mechanism of bone and joint destruction in rheumatoid arthritis.2007

    • Author(s)
      Miyazaki T, Tanaka S (1番目)
    • Journal Title

      Future Rheumatology 2

      Pages: 61-72

    • NAID

      10024377664

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Subcutaneous tendon rupture of extensor tendons on bilateral wrists associated with calcium pyrophosphate dihydrate crystal deposition disease.2007

    • Author(s)
      Ariyoshi D, Miyazaki T (他3名、ラスト)
    • Journal Title

      Mod Rheumatol 17

      Pages: 348-351

    • NAID

      10019865280

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Signaling axis in osteoclast biology and therapeutic targeting in the RANKL/RANK/OPG system.2007

    • Author(s)
      Tanaka S.
    • Journal Title

      Am J Nephrol. 27(5)

      Pages: 466-78

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Posttranslational regulation of Bim by Caspase-3 in the osteoclast.2007

    • Author(s)
      Wakeyama H, Tanaka S (他2名、ラスト)
    • Journal Title

      Ann N Y Acad Sci. [Epub ahead of print]

      Pages: 0-0

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of gammaglutamyltransferase in transgenic mice accelerates bone resorption and causes osteoporosis.2007

    • Author(s)
      Hiramatsu K, Tanaka S(他10名、9番目)
    • Journal Title

      Endocrinology. 148(6)

      Pages: 2708-15

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Scientific basis for the efficacy of combined use of antirheumatic drugs against bone destruction in rheumatoid arthritis.2007

    • Author(s)
      Suematsu A, Tanaka S (他7名、8番目)
    • Journal Title

      Mod Rheumatol. 17(1)

      Pages: 17-23

    • NAID

      10018733776

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The molecular mechanism of bone destruction in rheumatoid arthritis.2007

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

      Future Rheumatology 2

      Pages: 61-72

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Subcutaneous tendon rupture of extensor tendons on bilateral wrists associated with calcium pyrophosphate dihydrate crystal deposition disease.2007

    • Author(s)
      D Ariyoshi, K Imai, S Yamamoto, Y Kuga, T Miyazaki
    • Journal Title

      Modern Rheumatology 17

      Pages: 348-351

    • NAID

      10019865280

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Erk pathways negatively regulate matrix mineralization2007

    • Author(s)
      Kono SJ, Oshima Y, Hoshi K, Bonewald LF, Oda H, Nakamura K, Kawaguchi H, Tanaka S
    • Journal Title

      Bone 40

      Pages: 68-74

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

    • Author(s)
      Wakeyama H, Akiyama T, Takahashi K, Amano H, Kadono Y, Nakamura M, Oshima Y, Itabe H, Nakayama KI, Nakayama K, Nakamura K, Tanaka S.
    • Journal Title

      J Bone Miner Res 22

      Pages: 1631-1639

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Signaling axis in osteoclast biology and therapeutic targeting in the RANKL/RANK/OPG system.2007

    • Author(s)
      Tanaka S.
    • Journal Title

      Am J Nephrol 27

      Pages: 466-478

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ectodomain shedding of receptor activator of NF-kappaB ligand2007

    • Author(s)
      Hikita A, Tanaka S.
    • Journal Title

      Adv Exp Med Biol. 602

      Pages: 15-21

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Posttranslational regulation of Bim by Caspase-3 in the osteoclast.2007

    • Author(s)
      Wakeyama H, Akiyama T, Nakamura K, Tanaka S.
    • Journal Title

      Ann N Y Acad Sci. 1116

      Pages: 271-280

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [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2008

    • Author(s)
      土肥透、宮崎剛、山本精三、松井利浩、小宮明子、西野仁寿
    • Organizer
      第52回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Presentation] 骨・関節感染症における好中球上CD64 分子発現量計測の有用性2008

    • Author(s)
      西野仁寿、松井利浩、小宮明子、土肥透、宮崎剛、山本精三、松下隆
    • Organizer
      第52回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final 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Bcl-xL の機能解析2008

    • Author(s)
      岩澤三康、永瀬雄一、宮崎剛、門野夕峰、中村耕三、田中栄
    • Organizer
      第52回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌
    • Related Report
      2008 Final Research Report
  • [Presentation] 関節リウマチ患者の血漿PAD4値と抗PAD4抗体価の測定2008

    • Author(s)
      宮崎剛、山本精三
    • Organizer
      日本整形外科学会基礎学術集会
    • Place of Presentation
      京都
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [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2008

    • Author(s)
      土肥透, 宮崎剛, 山本精三, 松井利浩, 小宮明子, 西野仁寿
    • Organizer
      第52回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report
  • [Presentation] 骨・関節感染症における好中球上CD64分子発現量計測の有用性2008

    • Author(s)
      西野仁寿, 松井利浩, 小宮明子, 土肥透, 宮崎剛, 山本精三, 松下隆
    • Organizer
      第52回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report 2007 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Bcl-xLの機能解析2008

    • Author(s)
      岩澤三康, 永瀬雄一, 宮崎剛, 門野夕峰, 中村耕三, 田中栄
    • Organizer
      第52回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report
  • [Presentation] 骨粗鬆症が人工骨頭置換術におけるインプラントの固定性に与える影響についての検討2008

    • Author(s)
      近藤桃子, 山本精三, 穴水依人, 宮崎剛, 濱路博, 宮本恵成, 小泉英樹, 有吉大, 土肥透
    • Organizer
      第81回日本整形外科学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report
  • [Presentation] 人工股関節全置換術後ポリエチレンライナー内骨頭移動計測値における臥位と立位での差異およびその要因の検討2008

    • Author(s)
      濱路博, 山本精三, 石橋英明, 穴水依人, 宮崎剛
    • Organizer
      第81回日本整形外科学会学術総会
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report
  • [Presentation] 関節リウマチの骨・関節感染症治療における好中球CD64 値の有用性2007

    • Author(s)
      土肥透、宮崎剛、山本精三、西野仁寿
    • Organizer
      第35回日本リウマチ・関節外科学会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report
  • [Presentation] 両側伸筋腱断裂を生じた中高年発症のピロ燐酸カルシウム結晶沈着症の一例2007

    • Author(s)
      有吉大、山本精三、久我芳昭、宮崎剛
    • Organizer
      第51回日本リウマチ学会総会
    • Place of Presentation
      横浜
    • Related Report
      2008 Final Research Report
  • [Presentation] 両側伸筋腱断裂を生じた中高年発症のピロ燐酸力ルシウム結晶沈着症の一例2007

    • Author(s)
      有吉 大、山本 精三、久我 芳昭、宮崎 剛
    • Organizer
      第51回日本リウマチ学会総会・学術集会
    • Place of Presentation
      横浜
    • Related Report
      2007 Annual Research Report
  • [Presentation] 関節リウマチの骨・関節感染症治療における好中球CD64値の有用性2007

    • Author(s)
      土肥 透、宮崎 剛、山本 精三、松井 利浩、小宮 明子、西野 仁寿
    • Organizer
      第35回日本リウマチ・関節外科学会
    • Place of Presentation
      東京
    • Related Report
      2007 Annual Research Report
  • [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2007

    • Author(s)
      土肥 透、宮崎 剛、山本 精三、松井 利浩、小宮 明子、西野 仁寿
    • Organizer
      第52回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌
    • Related Report
      2007 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Bcl-xLの機能解析2007

    • Author(s)
      岩澤 三康、永瀬 雄一、宮崎 剛、門野 夕峰、中村 耕三、田中 栄
    • Organizer
      第52回日本リウマチ学会総会・学術集会
    • Place of Presentation
      札幌
    • Related Report
      2007 Annual Research Report
  • [Book] 骨疾患モデル動物実験ガイド。老化・老年病研究のための動物実験ガイド2008

    • Author(s)
      宮崎剛、岩澤三康
    • Publisher
      アドスリー
    • Related Report
      2008 Final Research Report
  • [Book] 老化・老年病研究のための動物実験ガイド2008

    • Author(s)
      宮崎 剛
    • Total Pages
      6
    • Publisher
      アドスリー
    • Related Report
      2007 Annual Research Report
  • [Book] 基礎老化研究2008

    • Author(s)
      宮崎 剛
    • Total Pages
      5
    • Publisher
      日本基礎老化学会
    • Related Report
      2007 Annual Research Report
  • [Book] Clinical Calcium2007

    • Author(s)
      田中 栄
    • Total Pages
      7
    • Publisher
      医薬ジャーナル社
    • Related Report
      2007 Annual Research Report
  • [Book] 炎症と免疫2007

    • Author(s)
      田中 栄
    • Total Pages
      5
    • Publisher
      先端医学社
    • Related Report
      2007 Annual Research Report
  • [Book] 生体の科学2007

    • Author(s)
      田中 栄
    • Total Pages
      6
    • Publisher
      医学書院
    • Related Report
      2007 Annual Research Report
  • [Book] 整形外科2007

    • Author(s)
      分山 秀敏、田中 栄
    • Total Pages
      1
    • Publisher
      南江堂
    • Related Report
      2007 Annual Research Report
  • [Book] 医学のあゆみ2007

    • Author(s)
      中村 正樹, 田中 栄
    • Total Pages
      4
    • Publisher
      医歯薬出版
    • Related Report
      2007 Annual Research Report
  • [Book] リウマチ科2007

    • Author(s)
      岩澤 三康, 田中 栄
    • Total Pages
      7
    • Publisher
      科学評論社
    • Related Report
      2007 Annual Research Report

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

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