Development of the prevention method for steroid-induced osteonecrosis using screening system of cell-free technology for protein analyses

• Project/Area Number: 15K15552
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Ehime University
• Principal Investigator: Imai Yuuki 愛媛大学, プロテオサイエンスセンター, 教授 (10423873)
• Co-Investigator(Renkei-kenkyūsha): SAWASAKI Tatsuya 愛媛大学, プロテオサイエンスセンター, 教授 (50314969)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 特発性大腿骨頭壊死 / ステロイド / グルココルチコイド / 大腿骨頭壊死

Outline of Final Research Achievements

To clarify the mechanism of the onset and progress of steroid-induced osteonecrosis of femoral head, we tried to identify the proteins interacting with Glucocorticoid Receptor (GR) using screening system of cell-free technology for protein analysis. As the results, we successfully identified more than 300 proteins, which interact with GR including not only reported proteins but also non-reported proteins relate to autophagy. This result indicates that steroid-induced osteonecrosis can be partly caused by protein degradation of non-genomic GR action as well as genomic actions.

Research Products

• [Journal Article] Co-administration of Systemic Zoledronate Promotes Osteogenesis Induced by a Local Co-delivery of Recombinant Human Bone Morphogenetic Protein-2 and Β-tricalcium Phosphate in the Bone Marrow of the Rabbit Femur (2017)
  • Author(s): Mamoto K, Ohta Y, Ichikawa K, Imai Y, Minoda Y, Takaoka K, Nakamura H.
  • Journal Title: J Musculoskelet Res. Volume: 19(3) Issue: 03 Pages: 1650015-1650015
  • DOI: 10.1142/s0218957716500159
  • Peer Reviewed
• [Journal Article] The CUL3-SPOP-DAXX axis is a novel regulator of VEGFR2 expression in vascular endothelial cells (2017)
  • Author(s): Sakaue T, Sakakibara I, Fujisaki A, Uesugi T, Nakashiro K, Hamakawa H, Kubota E, Joh T, Imai Y, Izutani H, Higashiyama S.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 42845-42845
  • DOI: 10.1038/srep42845
  • Peer Reviewed / Open Access
• [Journal Article] Local co-application of zoledronate promotes long-term maintenance of newly formed bone induced by recombinant human bone morphogenetic protein 2. (2016)
  • Author(s): Ichikawa K, Ohta Y, Mamoto K, Mizokawa S, Minoda Y, Imai Y, Takaoka K, Nakamura H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 480 Issue: 3 Pages: 314-320
  • DOI: 10.1016/j.bbrc.2016.10.034
  • Peer Reviewed
• [Journal Article] Identification of Nedd9 as a TGF-β-Smad2/3 Target Gene Involved in RANKL-Induced Osteoclastogenesis by Comprehensive Analysis (2016)
  • Author(s): Omata Y, Nakamura S, Koyama T, Yasui T, Hirose J, Izawa N, Matsumoto T, Imai Y, Seo S, Kurokawa M, Tsutsumi S, Kadono Y, Morimoto C, Aburatani H, Miyamoto T, Tanaka S.
  • Journal Title: PLoS One. Volume: 11 Issue: 6 Pages: e0157992-e0157992
  • DOI: 10.1371/journal.pone.0157992
  • Peer Reviewed / Open Access
• [Journal Article] sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss. (2016)
  • Author(s): Haraguchi R, Kitazawa R, Mori K, Tachibana R, Kiyonari H, Imai Y, Abe T, Kitazawa S.
  • Journal Title: Sci Rep. Volume: 6:25198 Issue: 1 Pages: 1-14
  • DOI: 10.1038/srep25198
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Epigenetic regulator, Uhrf1 ,is a positive regulator in chondrocyte differntiation (2016)
  • Author(s): Michiko Yamashita,Kazuki Inoue,Iori Sakakibara,Akari Murakami,Yoshiaki Kamei,Yuuki Imai
  • Organizer: 第13回国際人類遺伝学会
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Chromatin remodeling during osteoclast differentiation determined by DNase-seq. (2015)
  • Author(s): Yuuki Imai,Kazuki Inoue
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
  • Invited
• [Presentation] DNase-seqによる破骨細胞分化を制御する新規転写因子の同定 (2015)
  • Author(s): 今井祐記
  • Organizer: 第30回日本整形外科学会基礎学術集会
  • Place of Presentation: 富山市民プラザ（富山県富山市）
  • Year and Date: 2015-10-22
  • Invited
• [Presentation] アンドロゲンによる骨格筋増強機構の解明 (2015)
  • Author(s): 榊原伊織、今井祐記
  • Organizer: 第1回日本筋学会学術集会
  • Place of Presentation: 国立精神・神経医療研究センター（東京都小平市）
  • Year and Date: 2015-08-08
• [Presentation] 骨粗鬆症の病態生理と治療法的探索の試み (2015)
  • Author(s): 今井祐記
  • Organizer: 第25回日本病態生理学会
  • Place of Presentation: 愛媛大学南加記念ホール（愛媛県松山市）
  • Year and Date: 2015-07-31
  • Invited
• [Presentation] Big data解析を用いた細胞分化制御因子の同定 (2015)
  • Author(s): 今井祐記
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2015-07-23
  • Invited
• [Presentation] DNase-seqによる破骨細胞分化を制御する新規転写因子の同定 (2015)
  • Author(s): 井上和樹、今井祐記
  • Organizer: 第1回日本骨免疫学会
  • Place of Presentation: ホテルブリーズベイマリーナ（沖縄県宮古市）
  • Year and Date: 2015-06-30
• [Presentation] Inhibition of a cholesterol regulator, Srebp2, prevents RANKL-induced bone loss (2015)
  • Author(s): Kazuki Inoue, Yuuki Imai
  • Organizer: 4th Joint Meeting ECTS and IBMS
  • Place of Presentation: Rotterdam, Netherlands
  • Year and Date: 2015-04-25
  • Int'l Joint Research
• [Remarks] 愛媛大学プロテオサイエンスセンター病態生理解析部門ホームページ
  • URL: http://www.m.ehime-u.ac.jp/school/imailab
• [Remarks] 愛媛大学プロテオサイエンスセンター病態生理解析部門ホームページ
  • URL: http://www.m.ehime-u.ac.jp/school/imailab/publications.php