Luman, an ER membrane-bound transcription factor, is involved in osteoclastogenesis

• Project/Area Number: 25861324
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Hiroshima University
• Principal Investigator: KANEMOTO Soshi 広島大学, 医歯薬保健学研究院, 助教 (90611913)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 破骨細胞 / 小胞体 / 転写因子 / 分化 / 細胞融合

Outline of Final Research Achievements

Luman is a type II transmembrane transcription factor belonging to the OASIS family that localizes to the endoplasmic reticulum (ER) membrane under normal conditions. In response to ER stress, OASIS family members are processed, and cleaved N-terminal fragments translocate to the nucleus and function as a transcription factor. In this study, it was revealed that Luman is induced and activated during osteoclast differentiation. ShRNA-mediated knockdown of Luman prevents the formation of multinucleated osteoclasts, concomitant with the suppression of DC-STAMP, a protein essential for cell-cell fusion in osteoclastogenesis. N-terminus of Luman leads to up-regulation of DC-STAMP expression. Moreover, Luman interacts with DC-STAMP, and controls its stability and localization. These results suggest that Luman regulates the multinucleation of osteoclasts by promoting cell fusion of mononuclear osteoclasts through DC-STAMP induction and intracellular distribution during osteoclastogenesis.

Research Products

• [Journal Article] Targeting the endoplasmic reticulum in prion disease treatment: breakthroughs and challenges. (2015)
  • Author(s): Kanemoto S.
  • Journal Title: Research and Reports in Biochemistry Volume: 5 Pages: 31-38
  • DOI: 10.2147/rrbc.s74357
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Master Regulator for Chondrogenesis, Sox9, Regulates Transcriptional Activation of the ER Stress Transducer BBF2H7/CREB3L2 in Chondrocytes. (2014)
  • Author(s): Hino K, Saito A, Kido M, Kanemoto S, Asada R, Takai T, Cui M, Cui X, Imaizumi K.
  • Journal Title: Journal of Biological Chemistry Volume: 289 Issue: 20 Pages: 13810-13820
  • DOI: 10.1074/jbc.m113.543322
  • Peer Reviewed / Open Access
• [Journal Article] Proliferation, differentiation and amyloid-β production in neural progenitor cells isolated from TgCRND8 mice. (2014)
  • Author(s): Kanemoto S, Griffin J, Markham-Coultes K, Aubert I, Tandon A, George-Hyslop PS, Fraser PE.
  • Journal Title: Neuroscience Volume: 261 Pages: 52-9
  • DOI: 10.1016/j.neuroscience.2013.12.021
  • Peer Reviewed
• [Journal Article] Chondrocyte Proliferation Regulated by Secreted Luminal Domain of ER Stress Transducer BBF2H7/CREB3L2. (2014)
  • Author(s): Saito A, Kanemoto S, Zhang Y, Asada R, Hino K, Imaizumi K.
  • Journal Title: Molecular Cell Volume: 53 Issue: 1 Pages: 127-139
  • DOI: 10.1016/j.molcel.2013.11.008
  • Peer Reviewed / Open Access
• [Journal Article] Increased Susceptibility to Dextran Sulfate Sodium-Induced Colitis in the Endoplasmic Reticulum Stress Transducer OASIS Deficient Mice. (2014)
  • Author(s): Hino K, Saito A, Asada R, Kanemoto S, Imaizumi K.
  • Journal Title: PLOS ONE Volume: 9 Issue: 2 Pages: e88048-e88048
  • DOI: 10.1371/journal.pone.0088048
  • Peer Reviewed / Open Access
• [Presentation] 小胞体膜局在転写因子Lumanによる破骨細胞分化制御機構の解明 (2014)
  • Author(s): 金本聡自、小林 泰浩、山下 照仁、宮本健史、高橋 直之、今泉和則
  • Organizer: 日本生化学会
  • Place of Presentation: 京都市
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Luman, an ER membrane-bound transcription factor, is involved in osteoclastogenesis (2014)
  • Author(s): Soshi Kanemoto, Yasuhiro Kobayashi, Teruhito Yamashita, Takeshi Miyamoto, Naoyuki Takahashi, Kazunori Imaizumi
  • Organizer: Bone Biology Forum
  • Place of Presentation: 静岡県裾野市
  • Year and Date: 2014-08-22 – 2014-08-23
  • Invited
• [Presentation] 小胞体膜局在転写因子Lumanは破骨細胞分化制御に関与する (2014)
  • Author(s): 金本聡自、小林 泰浩、山下 照仁、宮本健史、高橋 直之、今泉和則
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪市
  • Year and Date: 2014-07-24 – 2014-07-26
  • Invited
• [Presentation] 小胞体ストレスセンサーLumanは破骨細胞分化制御に関与する (2013)
  • Author(s): 金本聡自、齋藤敦、小林 泰浩、山下 照仁、宮本健史、高橋 直之、今泉和則
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 神戸市
• [Presentation] Luman, an ER stress transducer, is involved in osteoclastogenesis through the regulation of DC-STAMP expression. (2013)
  • Author(s): Soshi Kanemoto, Atsushi Saito, Yasuhiro Kobayashi, Teruhito Yamashita, Takeshi Miyamoto, Naoyuki Takahashi, Kazunori Imaizumi
  • Organizer: The 23rd ANZBMS Annual Scientific Meeting
  • Place of Presentation: Melbourne, Australia