Analysis of novel MAP kinase binding factor which regulates osteoclasts

• Project/Area Number: 19592163
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Matsumoto Dental University
• Principal Investigator: YAMASHITA Teruhito Matsumoto Dental University, 総合歯科医学研究所, 講師 (90302893)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Naoyuki 松本歯科大学, 大学院歯学独立研究科, 教授 (90119222) ; NINOMIYA Tadashi 松本歯科大学, 総合歯科医学研究所, 講師 (00360222) ; MIZOGUCHI Toshihide 松本歯科大学, 総合歯科医学研究所, 講師 (90329475)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 破骨細胞 / MAPキナーゼ / 骨吸収

Research Abstract

サイトカインの分泌や細胞生存に重要なp38 MAPキナーゼ経路を抑制的に制御する因子が破骨細胞で高発現しているという仮説の元、MKK6結合因子Alixを新規に同定し、破骨細胞におけるその機能の解析を行った。その結果、AlixはMKK6に結合してp38 MAPキナーゼの活性化を抑制することを明らかにした。しかし、Alixの発現を抑制しても、破骨細胞の生存の亢進やサイトカインの再分泌は見られなかった。

Research Products

• [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo. (2009)
  • Author(s): Mizoguchi T, Muto A, Udagawa N, Arai A, Yamashita T, Hosoya A, Ninomiya T, Nakamura H, Yamamoto Y, Kinugawa S, Nakamura M, Nakamichi Y, Kobayashi Y, Nagasawa S, Oda K, Tanaka H, Tagaya M, Penninger JM, Ito M, Takahashi N
  • Journal Title: J Cell Biol 184 Pages: 541-554
  • Peer Reviewed
• [Journal Article] Docetaxel inhibits bone resorption through suppression of osteoclast formation and function in different manners. (2009)
  • Author(s): Takahashi M, Mizoguchi T, Uehara S, Nakamichi Y, Yang S, Naramoto H, Yamashita T, Kobayashi Y, Yamaoka M, Furusawa K, Udagawa N, Uematsu T, Takahashi N
  • Journal Title: J Bone Miner Metab 27 Pages: 24-35
  • NAID: 10025336084
  • Peer Reviewed
• [Journal Article] Identification of cell cycle-arrested quiescent osteoclast precursors in vivo. (2009)
  • Author(s): Mizoguchi T, et al.
  • Journal Title: J Cell Biol 184 Pages: 541-554
  • Peer Reviewed
• [Journal Article] Docetaxel inhibits bone resorption through suppression of osteoclast formation and function in different manners. (2009)
  • Author(s): Takahashi M, et al.
  • Journal Title: J Bone Miner Metab 27 Pages: 24-35
  • NAID: 10025336084
  • Peer Reviewed
• [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
  • Peer Reviewed
• [Journal Article] MKK6-p38 MAPK signaling pathway enhances survival but not bone-resorbing activity of osteoclasts. (2008)
  • Author(s): Yamashita T, et. al.
  • Journal Title: Biochem Biophys Res Commun 365 Pages: 252-257
  • Peer Reviewed
• [Journal Article] Signal transduction of lipopolysaccharide- induced osteoclast differentiation. (2007)
  • Author(s): Udagawa N, Sato N, Yang S, Nakamura M, Yamashita T, Nakamura H, Noguchi T
  • Journal Title: Periodontology 2000 43 Pages: 56-64
  • Peer Reviewed
• [Journal Article] NF-{kappa}B p50 and p52 Regulate Receptor Activator of NF-{kappa}B Ligand(RANKL)and Tumor Necrosis Factor-induced Osteoclast Precurs or Differentiation by Activating c-Fos and NFATcl. (2007)
  • Author(s): Yamashita T, et. al.
  • Journal Title: J Biol Chem 282 Pages: 18245-18253
  • Peer Reviewed
• [Journal Article] Signal transduction of lipopolysaccharide-induced osteoclast differentiation. (2007)
  • Author(s): Udagawa N, et. al.
  • Journal Title: Periodontol 2000 43 Pages: 56-64
  • Peer Reviewed
• [Journal Article] Generation of osteoclasts in vitro, and assay of osteoclast activity (2007)
  • Author(s): Takahashi N, et. al.
  • Journal Title: Methods Mol Med 135 Pages: 285-301
  • Peer Reviewed
• [Presentation] 破骨細胞分化に特化した静止期前駆細胞(QOP)は末梢血に存在し骨組織に遊走する (2008)
  • Author(s): 武藤昭紀, 他
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪市大阪国際会議場
  • Year and Date: 2008-10-31
• [Presentation] 破骨細胞のMAPキナーゼp38経路を制御する因子Alixの同定 (2007)
  • Author(s): 山下照仁、溝口利英、小林泰浩、二宮 禎、宇田川信之、高橋直之
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪市大阪国際会議場
  • Year and Date: 2007-07-21
• [Presentation] In vivoにおいて細胞周期の停止した破骨細胞前駆細胞(pOCP)は5-FU非感受性である (2007)
  • Author(s): 溝口利英、武藤昭紀、細矢明宏、中道裕子、山下照仁、小林泰浩、宇田川信之、伊藤充雄、高橋直之
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪市大阪国際会議場
  • Year and Date: 2007-07-21
• [Presentation] 破骨細胞のMAPキナーゼp38経路を制御する因子Alixの同定 (2007)
  • Author(s): 山下照仁, 他
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪市 大阪国際会議場
  • Year and Date: 2007-07-21
• [Presentation] In vivoにおいて細胞周期の停止した破骨細胞前駆細胞(pOCP)は5-FU非感受性である (2007)
  • Author(s): 溝口利英, 他
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪市 大阪国際会議場
  • Year and Date: 2007-07-21