The elucidation of miRNAs in response to stress stimuli and its secretion into an oral cavity

• Project/Area Number: 25670822
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: The University of Tokushima
• Principal Investigator: ICHIKAWA Tetsuo 徳島大学, ヘルスバイオサイエンス研究部, 教授 (90193432)
• Co-Investigator(Kenkyū-buntansha): YOSHIMOTO Katsuhiko 徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授 (90201863) ; TOMOTAKE Yoritoki 徳島大学, 病院, 准教授 (70263853) ; MIZUSAWA Noriko 徳島大学, 大学院ヘルスバイオサイエンス研究部, 助教 (80254746)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: microRNA / メカニカルストレス / 細胞増殖 / MC3T3-E1細胞 / micro-RNA / 圧縮応力 / 骨芽細胞 / miR-494-3p / Fgfr2 / Rock1 / ストレス負荷 / 圧縮力 / マイクロアレイ解析 / FGFR2

Outline of Final Research Achievements

In the present study, we attempted to identify miRNA in response to mechanical stress in MC3T3-E1 cells, a mouse osteoblast-like cell line, and to elucidate its functions.
We identified miRNAs whose expression was changed in MC3T3-E1 cells subjected to compressive force at 294 Pa for 24 h. Treatment with compressive force and overexpression of miR-494-3p, a miRNA up-regulated by compressive force, in MC3T3-E1 cells inhibited the cell proliferation. Furthermore, we demonstrated that Fgfr2 and Rock1 were targets of mi494-3p in MC3T3-E1 cells, and their knockdown inhibited the cell proliferation.
We concluded that compressive force affected expressions of several miRNAs including miR-494-3p in MC3T3-E1 cells. Compressive force might inhibit cell proliferation in MC3T3-E1 cells by up-regulating miR-494-3p followed by Fgfr2 and Rock1 gene repressions. For further study, we will investigate whether these miRNAs induced by compressive force exist in saliva.

Research Products

• [Journal Article] MiR-494-3p induced by compressive force inhibits cell proliferation in MC3T3-E1 cells (2015)
  • Author(s): Yuki Iwawaki, Noriko Mizusawa, Takeo Iwata, Nobuaki Higaki, Takaharu Goto, Megumi Watanabe, Yoritoki Tomotake, Tetsuo Ichikawa, Katsuhiko Yoshimoto
  • Journal Title: Journal of Bioscience and Bioengineering Volume: 120 Issue: 4 Pages: 456-462
  • DOI: 10.1016/j.jbiosc.2015.02.006
  • NAID: 110010010230
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Mechanical stress - responsive micro-RNA (2014)
  • Author(s): Yuki Iwawaki, Noriko Mizusawa, Tomotake Yoritoki, Ichikawa Testuo, Katuhiko Yoshimoto
  • Organizer: The 3rd ASEAN plus and TOKUSHIMA Joint International Conference on “Strategic Achievement of Oral Sciences and Promotion of Quality of Life”
  • Place of Presentation: Makassar (Indonesia)
  • Year and Date: 2014-12-04
• [Presentation] メカニカルストレス応答性miR-494-3pによるFGFR2発現の抑制 (2014)
  • Author(s): 岩脇有軌、水澤典子、小野信二、岩田武男、吉本勝彦
  • Organizer: 第56回歯科基礎医学会学術大会・総会
  • Place of Presentation: 福岡国際会議場(福岡県福岡市）
  • Year and Date: 2014-09-26 – 2014-09-27
• [Presentation] メカニカルストレス応答性micro-RNA - miR-494-3pはFGFR2の発現を抑制する- (2014)
  • Author(s): 岩脇有軌、水澤典子、水頭英樹、後藤崇晴、渡邉 恵、友竹偉則、市川哲雄
  • Organizer: 公益社団法人日本補綴歯科学会第123回学術大会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2014-05-24 – 2014-05-25
• [Presentation] メカニカルストレス応答性micro-RNA － miR-494-3pはFGFR2の発現を抑制する - (2014)
  • Author(s): 岩脇有軌、水澤典子、水頭英樹、後藤崇晴、渡邉恵、友竹偉則、市川哲雄
  • Organizer: 公益社団法人日本補綴歯科学会第123回学術大会
  • Place of Presentation: 宮城県仙台市:仙台国際センター
• [Presentation] 機械的刺激応答性miRNAの同定 (2013)
  • Author(s): 岩脇有軌、水澤典子、岩田武男、小野信二、友竹偉則、市川哲雄、吉本勝彦
  • Organizer: 第5回 日本RNAi研究会
  • Place of Presentation: 広島県広島市:グランドプリンスホテル広島
• [Presentation] メカニカルストレスに応答するmicroRNAの同定 (2013)
  • Author(s): 岩脇有軌、後藤崇晴、渡邉恵、友竹偉則、市川哲雄
  • Organizer: 第43回公益社団法人日本口腔インプラント学会・学術大会
  • Place of Presentation: 福岡県福岡市:福岡国際会議場