Functional analysis of Arkadia in bone metabolism using innovative imaging technique and KO mice

• Project/Area Number: 15K15553
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Ehime University
• Principal Investigator: Takeshi Imamura 愛媛大学, 医学系研究科, 教授 (70264421)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: バイオテクノロジー / シグンル伝達 / 遺伝子 / タンパク質 / 細胞・組織

Outline of Final Research Achievements

To identify the cofactor controlling Arkadia and to elucidate its molecular mechanism, screening of Arkadia binding protein was performed to obtain a candidate gene. Smad6 was identified as a new Arkadia target protein, Arkadia promotes differentiation by predominantly activating BMP signal during the late stage differentiation of osteoblasts, and ubiquitinates Smad6 which selectively suppresses BMP signal leading to degradation. A marked abnormality was found in the knockout mouse of E3 ubiquitin ligase Smurf 2 that negatively regulates the BMP signal prepared as a comparison target of Arkadia analysis.

Research Products

• [Journal Article] Quantitative imaging of fibrotic and morphological changes in liver of non-alcoholic steatohepatitis (NASH) model mice by second harmonic generation (SHG) and auto-fluorescence (AF) imaging using two-photon excitation microscopy (TPEM). (2016)
  • Author(s): Yamamoto S, Oshima Y, Saitou T, Watanabe T, Miyake T, Yoshida O, Tokumoto Y, Abe M, Matsuura B, Hiasa Y, Imamura T
  • Journal Title: Biochemistry and Biophysics Reports Volume: 8 Pages: 277-283
  • DOI: 10.1016/j.bbrep.2016.09.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Arkadia enhances BMP signaling through ubiquitylation and degradation of Smad6 (2015)
  • Author(s): Tsubakihara Y, Hikita A, Yamamoto S, Matsushita S, Matsushita N, Oshima Y, Miyazawa K, Imamura T
  • Journal Title: The Journal of Biochemistry Volume: 158(1) Issue: 1 Pages: 61-71
  • DOI: 10.1093/jb/mvv024
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 骨・軟骨イメージングのための顕微鏡開発 (2016)
  • Author(s): 今村健志
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡市、福岡国際会議場
  • Year and Date: 2016-10-13
  • Invited
• [Presentation] In vivo cancer imaging by advanced multi-photon laser excitation microscopy (2016)
  • Author(s): Takeshi Imamura
  • Organizer: The 41st Naito Conference on Cancer Heterogeneity and Plasticity: Relevance to Therapeutic Resistance
  • Place of Presentation: 札幌市、シャトレーゼガトーキングダムサッポロ
  • Year and Date: 2016-07-05
  • Int'l Joint Research / Invited
• [Presentation] Development and application of advanced intravital imaging technique in oncology and lymphology (2016)
  • Author(s): Takeshi Imamura
  • Organizer: The 40th Annual meeting of the Japanese Society of Lymphology
  • Place of Presentation: Ito International Research Center, The University of Tokyo
  • Year and Date: 2016-06-24
  • Invited
• [Presentation] 脳神経外科手術応用を目指した革新的バイオイメージング技術開発 (2016)
  • Author(s): 今村健志
  • Organizer: 第16回日本術中画像情報学会
  • Place of Presentation: 愛媛県松山市、松山全日空ホテル
  • Invited
• [Presentation] 先端的バイオイメージング技術の薬理学応用 (2016)
  • Author(s): 今村健志
  • Organizer: 第69回日本薬理学会西南部会
  • Place of Presentation: 愛媛県松山市、松山大学
  • Invited