Molecular mechanisms of NF-kB in regulating stem cells

• Project/Area Number: 26293421
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Niigata University
• Principal Investigator: Ohazama Atsushi 新潟大学, 医歯学系, 教授 (40266169)
• Co-Investigator(Kenkyū-buntansha): 前田 健康 新潟大学, 医歯学系, 教授 (40183941) ; 井上 佳世子 (野澤佳世子 / 井上 佳世子(野澤佳世子)) 新潟大学, 医歯(薬)学総合研究科, 准教授 (90303130) ; 河野 芳朗 新潟大学, 医歯学系, 助教 (60303129)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000); Fiscal Year 2016: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
• Keywords: 歯の発生 / 幹細胞 / NF-kB / 歯 / 幹細胞ニッチ

Outline of Final Research Achievements

Nuclear factor kappa B (NF-κ B) signaling plays critical roles in many physiological and pathological processes, including regulating organogenesis. It has been shown that NF-κB signaling regulate tooth development from initiation to the late stage. The roles of NF-κB signaling in regulating dental stem cells, however, are not fully understood. Our results using mice overexpressing IKKβ, an essential component of the NF-κ B pathway, under keratin 5 promoter suggested that over-activation of NF-kB signaling lead to supernumerary incisors by abnormal Wnt signaling activity and apoptosis in embryonic lower incisor tooth epithelium. Excess NF-κB activity thus induces an ectopic odontogenesis program that is usually suppressed under physiological conditions. NF-kB signaling is also found to control homeostasis of stem cell in the cervical loop, which is regulated by different molecular mechanisms from those in embryonic tooth germ.

Research Products

• [Journal Article] Expression of Sox genes in tooth development. (2015)
  • Author(s): Kawasaki K, Kawasaki M, Watanabe M, Idrus E, Nagai T, Oommen S, Maeda T, Hagiwara N, Que J, Sharpe PT, Ohazama A.
  • Journal Title: Int J Dev Biol. Volume: 59(10-12) Issue: 10-11-12 Pages: 471-478
  • DOI: 10.1387/ijdb.150192ao
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Excess NF-kB induces ectopic odontogenesis in embryonic incisor epithelium. (2015)
  • Author(s): Blackburn, J., Kawasaki, K., Porntaveetus, T., Kawasaki, M., Otsuka-Tanaka, Y., Miake, Y., Ota, M.S., Watanabe, M., Hishinuma, M., Nomoto, T., Oommen, S., Ghafoor, S., Harada, F., Nozawa-Inoue, K., Maeda, T., Peterková, R., Lesot, H., Inoue, J., Akiyama, T.,
  • Journal Title: J. Dent. Res Volume: 94 Issue: 1 Pages: 121-128
  • DOI: 10.1177/0022034514556707
  • Peer Reviewed / Open Access