Analysis of the role of mechanosensor-mediated JNK/p38 signaling in osteoimmunological regulation of osteoblasts

• Project/Area Number: 24792059
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Prosthetic dentistry
• Research Institution: Tohoku University
• Principal Investigator: MATSUI Hiroyuki 東北大学, 大学病院, 医員 (10547277)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: メカノバイオロジー / 骨代謝 / JNK / p38 / ERK / メカノトランスダクション / ストレス応答MAPキナーゼ / 骨免疫学

Research Abstract

In this study, we report that large-magnitude (12%) cyclic stretch induced Ca2+ influx in MC3T3-E1 osteoblasts, which subsequently activated ASK1 MAP3K. The activated ASK1-JNK lead to transiently enhanced expression of FGF-inducible 14 (Fn14, a member of the TNF receptor superfamily) gene. Cells with enhanced expression of Fn14 subsequently acquired sensitivity to the ligand of Fn14, TNF-related weak inducer of apoptosis, and underwent apoptosis. On the other hand, ASK1-p38 pathway induced expression of monocyte chemoattractant protein-3 (MCP-3) gene, which promoted chemotaxis of pre-osteoclasts. These results suggest that ASK1-JNK/p38 pathways contribute to the mechanism of mechanical overloading-induced bone resroption via cytokine-related gene expression.

Research Products

• [Journal Article] The expression of Fn14 via mechannical stress-activated JNK contributes to apoptosis induction in osteoblasts (2014)
  • Author(s): Matsui H., Fukuno N., Kanda Y., Kantoh Y., Chida T., Nagaura Y., Suzuki O., Nishitoh H., Takeda K., Ichijo H., Sawada Y., Sasaki K., Kobayashi T., and Tamura S
  • Journal Title: J. Biol. Chem Volume: 289 Pages: 6438-6450
  • Peer Reviewed
• [Journal Article] The expression of Fn14 via mechanical stress-activated JNK contributes to apoptosis induction in osteoblasts. (2014)
  • Author(s): Matsui, H., Fukuno, N., Kanda, Y., Kantoh, Y., Chida, T., Nagaura, Y., Suzuki, O., Nishitoh, H., Takeda, K., Ichijo, H., Sawada, Y., Sasaki, K., Kobayashi, T. and Tamura, S.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 10 Pages: 6438-6450
  • DOI: 10.1074/jbc.m113.536300
  • Peer Reviewed / Open Access
• [Journal Article] Acyl-CoA binding domain containing 3 (ACBD3) recruits the protein phosphatase PPM1L to ER-Golgi membrane contact sites (2012)
  • Author(s): Shinoda Y, Fujita K, Saito S, Matsui H, Kanto Y, Nagaura Y, Fukunaga K, Tamura S, Kobayashi T
  • Journal Title: FEBS Letters Volume: 586(19) Pages: 3024-9
  • Peer Reviewed
• [Journal Article] Src, p130Cas, and Mechanotransduction in Cancer Cells (2012)
  • Author(s): Matsui H, Harada I and Sawada Y
  • Journal Title: Genes and Cancer Volume: 3(5-6) Pages: 394-401
  • Peer Reviewed
• [Journal Article] メカニカルストレスと変形性関節症 (2012)
  • Author(s): 松井裕之, 原田伊知郎, 石島旨章, 澤田泰宏
  • Journal Title: CLINICAL CALCIUM Volume: Vol.22 No.12(doi:CliCa121218551862) Pages: 1855-1862
  • Peer Reviewed
• [Journal Article] Src, p130Cas and mechanotransduction in Cancer Cells. (2012)
  • Author(s): Matsui H, Harada I, and Sawada Y
  • Journal Title: Genes and Cancer Volume: 3 Issue: 5-6 Pages: 394-401
  • DOI: 10.1177/1947601912461443
  • Peer Reviewed
• [Book] イラストで徹底理解するシグナル伝達キーワード事典 (2012)
  • Author(s): 編集 山本 雅, 仙波憲太郎, 山梨裕司 著者 松井裕之, 他
  • Publisher: 羊土社
• [Book] イラストで理解するシグナル伝達キーワード辞典 (2012)
  • Author(s): 松井裕之 他
  • Publisher: 羊土社
• [Book] CLINICAL CALCIUM (2012)
  • Author(s): 松井裕之、原田伊知郎、石島旨章、澤田泰宏
  • Publisher: 医薬ジャーナル