Regulation of Bone metabolism by JNK signaling

• Project/Area Number: 19791019
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: NAKAMURA Takashi Tokyo Medical and Dental University, 難治疾患研究所, 助教 (80431948)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: ストレス / JNK / SEK1 / MKK4 / MKK7 / 骨 / 遺伝子破壊 / リン酸化 / MAPキナーゼ / ノックアウトマウス / Sekl / Mkk4

Research Abstract

本研究ではストレスシグナル伝達系である、MKK-JNKシグナル経路の骨細胞における生体内高次機能の解明を目的として研究を進める。具体的には、1)骨細胞特異的な時期特異的遺伝子破壊システムの構築と条件付きSEK1遺伝子破壊マウス系統の樹立を行う。続いて、これらマウス系統を交配する事で 2)骨細胞特異的SEK1,MKK7 遺伝子破壊マウスの作出を行い、ストレス応答性シグナル伝達分子の骨組織での高次機能について解析を行う。さらに、ストレス応答経路の分子機構を解明する事により、3)骨組織の重力ストレス感知機構における新規分子標的の同定を目的とする。これまでにMKK7遺伝子破壊マウスの作出され、成長遅延の表現型が観察されており、骨組織への影響も生じていると考えられる。本マウスの詳細な解析により、本シグナルの新たな生理機能が解明されると期待される。

Research Products

• [Journal Article] Hematopoiesis-dependent expression of CD44 in murine hepatic progenitor cells (2009)
  • Author(s): Shinya Ohata, Makiko Nawa, Takeshi Kasama, Tokiwa Yamasaki, Kenji Sawanobori, Shoji Hata, Takashi Nakamura, Yoichi Asaoka, Tomomi Watanabe, Hitoshi Okamoto, Takahiko Hara, Shuji Terai, Isao Sakaida, Toshiaki Katada, Hiroshi Nishina
  • Journal Title: Biochem Biophys Res Commun. 20; 379(4) Pages: 817-23
  • Peer Reviewed
• [Journal Article] Hematopoiesis-dependent expression of CD44 in murine hepatic progenitor cells (2009)
  • Author(s): Shinya Ohata, et.al.
  • Journal Title: Biochem. Biophys. Res. Commun 379 Pages: 817-823
  • Peer Reviewed
• [Journal Article] A histone lysine methyltransferase activated by non-canonical Wnt signaling suppresses PPAR-gamma transactivation (2007)
  • Author(s): Ichiro Takada, Masatomo Mihara, Miyuki Suzawa, Fumiaki Ohtake, Shinji Kobayashi, Mamoru Igarashi, Ken-ichi Takeyama, Min-Young Youn, Takashi Nakamura, Yoshihiro Mezaki, Shin-ichiro Takezawa, Yoshiko Yogiashi, Hirochika Kitagawa, Gen Yamada, Shinji Takada, Yasuhiro Minami, Hiroshi Shibuya, Kunihiro Matsumoto, Shigeaki Kato
  • Journal Title: Nat Cell Biol 9,(11) Pages: 1273-1285
  • Peer Reviewed
• [Journal Article] Osteoclastic estrogen receptor alpha mediates the osteoprotective estrogen action through Fas ligand signaling (2007)
  • Author(s): Takashi Nakamura, Yuuki Imai, Takahiro Matsumoto, Singo Sato, Kazusane Takeuchi, Katsuhide Igarashi, Yoshifumi Harada, Yoshiaki Azuma, Andree Krust, Yoko Yamamoto, Hiroshi Nishina, Shu Takeda, Hiroshi Takayanag, Daniel Metzger, Jun Kanno, Kunio Takaoka, T. John Martin, Pierre Chambon, Shigeaki Kato
  • Journal Title: Cell 130(5) Pages: 811-823
  • Peer Reviewed
• [Journal Article] Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice (2007)
  • Author(s): Ken-ichi Aihara, Hiroyuki Azuma, Masashi Akaike, Yasumasa Ikeda, Masataka Sata, Nobuyuki Takamori, Shunsuke Yagi, Takashi Iwase, Yuka Sumitomo, Hirotaka Kawano, Takashi Yamada, Toru Fukuda, Takahiro Matsumoto, Keisuke Sekine, Takashi Sato, Yuko Nakamichi, Yoko Yamamoto, Kimihiro Yoshimura, Tomoyuki Watanabe, Takashi Nakamura, Akimasa Oomizu, Miniru Tsukada, Hideki Hayashi, Toshiki Sudo, Shigeaki Kato, Toshio Matsumoto
  • Journal Title: J Clin Invest 117(6) Pages: 1514-1526
  • Peer Reviewed
• [Journal Article] DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs (2007)
  • Author(s): Toru Fukuda, Kaoru Yamagata, Sally Fujiyama, Takahiro Matsumoto, Iori Koshida, Kimihiro Yoshimura, Masatomo Mihara, Masanori Naitou, Hideki Endoh, Takashi Nakamura, Chihiro Akimoto, Yoko Yamamoto, Takenobu Katagiri, Charles Foulds, Shin-ichiro Takezawa, Hirochika Kitagawa, Ken-ichi Takeyama, Bert W. O'malley, Shigeaki Kato
  • Journal Title: Nat Cell Biol. 9(5) Pages: 604-611
  • Peer Reviewed
• [Journal Article] Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts (2007)
  • Author(s): Takashi Nakamura, et. al.
  • Journal Title: Cell 130 Pages: 811-823
  • Peer Reviewed
• [Journal Article] A histone lysine methyltransferase activated by non-canonical Wnt signaling suppresses PPAR-gamma transactivation (2007)
  • Author(s): Ichiro Takada, et. al.
  • Journal Title: Nature Cell Biology 9 Pages: 1273-1285
  • Peer Reviewed
• [Journal Article] Strain-dependent embryonic lethality and exaggerated vascular remodeling in heparin cofactor II-deficient mice (2007)
  • Author(s): Ken-ichi Aihara, et. al.
  • Journal Title: Journal of Clinical Investigation 117 Pages: 1514-1526
  • Peer Reviewed
• [Journal Article] DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of MicroRNAs (2007)
  • Author(s): Toru Fukuda, et. al.
  • Journal Title: Nature Cell Biology 9 Pages: 604-611
  • Peer Reviewed
• [Presentation] Transcriptional regulation of Steroid Action (2007)
  • Author(s): Shigeaki Kato, Takashi Nakamura, Takashi Sato, Yoko Yamamoto
  • Organizer: 2nd Conference on Skeletal Biology and Medicine
  • Place of Presentation: New York
  • Year and Date: 2007-04-27
• [Remarks] ホームページ等
  • URL: http://www.tmd.ac.jp/mri/dbio/index.html
• [Remarks]
  • URL: http://www.tmd.ac.jp/mri/dbio/index.html#