Evaluation on oxidative stress and damage of body-defense-cells caused by monomers and consideration of protective methods

• Project/Area Number: 16K11630
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Prosthodontics/ Dental materials science and
• Research Institution: Iwate Medical University
• Principal Investigator: TAIRA MASAYUKI 岩手医科大学, 歯学部, 准教授 (60179398)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 歯科用モノマー / トリエチレングリコールジメタクリレート / 単球 / グルタチオン / 解毒 / 抗酸化 / 炎症性サイトカイン / LPS / THP-1 / マクロファージ / 安全性評価 / 酸化ストレス / 活性酸素種 / 単球細胞 / フォルボールエステル / 解毒化酵素 / 歯学 / モノマー / シグナル伝達 / ストレス / 生理活性

Outline of Final Research Achievements

Monomers in dental resins irritate oral tissues. The purpose of this study was to evaluate effects of IC50 tri-ethelenglycol di-metahcrylate (TEGDMA) on gene expressions of lipopolysaccharide (LPS)-stimulated monocytic THP-1 cells. We compared gene expressions of two samples, namely (i) THP-1 cells stimulated with LPS for 4h (Control) and (ii) those exposed to IC50 TEGDMA for 24h and LPS for last 4h (Test) by DNA microarray analyses. Thirty four genes of Test were up-regulated more than 5-fold, relative to those of Control (p<0.05). The up-regulated genes of Test had two characteristic biological processes, namely xenobiotic metabolism (e.g. AKR1C1 and GSTA4 genes) and anti-oxidative stress (e.g. NQO1, GPX3, and SELM genes). These gene expressions were confirmed by quantitative real-time RT-PCR analyses.

Academic Significance and Societal Importance of the Research Achievements

TEGDMAモノマー単独作用下およびLPSとモノマーの二重作用下での単球（THP-1）の細胞内傷害作用（酸化ストレス傷害、炎症性サイトカイン傷害、モノマー分解産物傷害）を遺伝子発現から明らかにしたことは学術的に意義があると考えられた。TEGDMAモノマーによる単球の細胞内障害を還元型グルタチオンの薬物代謝と枯渇による酸化ストレスとの関係で考察する試みは有益と思われた。モノマーによる口腔組織への為害性の減少については、細胞内でグルタチオンを補充することが有効と考えられ、そのための薬物投与法の開発が期待された。

Research Products

• [Journal Article] Ectopic bone formation in muscles using injectable bone-forming material consisting of cross-linked hyaluronic acid, bone morphogenetic protein, and nano-hydroxyapatite (2019)
  • Author(s): Ikeda K, Sugawara S, Taira M, Sato H, Hatakeyama W, Kihara H, Kondo H.
  • Journal Title: Nano Biomedicine Volume: 11 Pages: 11-20
  • NAID: 130007687555
  • Peer Reviewed / Open Access
• [Journal Article] Loading of fluvastatin onto gelatin-coated titanium implants. (2018)
  • Author(s): Takemoto S, Sasaki K, Sugawara S, Saitoh S, Sawada T, Taira M, Tanabe K, Yoshinari M, Hattori M, Jansen JA, Leeuwenburgh SGG.
  • Journal Title: Key Engineering Materials Volume: 782 Pages: 233-237
  • Peer Reviewed
• [Journal Article] Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture (2017)
  • Author(s): Takizawa N, Okubo N, Kamo M, Chosa N, Mikami T, Suzuki K, Yokota S, Ibi M, Ohtsuka M, Taira M, Sasaki D, Yaegashi T, Ishisaki A, Kyakumoto S
  • Journal Title: Experimental Cell Res. Volume: 358 Issue: 2 Pages: 411-420
  • DOI: 10.1016/j.yexcr.2017.07.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bone regeneration of rat critical-size calvarial defects using a collagen/porous-apatite composite: Micro-CT analyses and histological observations (2017)
  • Author(s): Hatakeyama W, Taira M, Ikeda K, Sato H, Kihara H, Tekemoto S, Kondo H.
  • Journal Title: J Oral Tissue Engin. Volume: 15 Pages: 49-60
  • NAID: 130006394589
  • Peer Reviewed / Open Access
• [Journal Article] Effects of addition of nano-hydroxyapatite to highly-pressed collagen on osteogenic differentiation in osteoblastic SaOS-2 cells. (2016)
  • Author(s): Ikeda K., Taira M, Yokota J, Hattori M, Ishisaki A, Kondo H.
  • Journal Title: Nano Biomedicine Volume: 8 Pages: 91-100
  • NAID: 130005243671
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] スタチン系薬剤を固定したチタンの薬剤徐放特性 (2019)
  • Author(s): 武本 真治，澤田 智史，畑中 昭彦，平 雅之
  • Organizer: 第49回日本口腔インプラント学会
• [Presentation] ろう付けしたステンレス鋼の酸性溶液中での溶出挙動 (2019)
  • Author(s): 齋藤設雄，佐々木かおり，澤田智史，畑中昭彦，平 雅之，武本真治
  • Organizer: 74回日本歯科理工学会学術講演会
• [Presentation] 重度インプラント周囲炎に対し外科的デブライトメントと自家骨移植を併用した症例 (2018)
  • Author(s): 菅原志帆，畠山 航，高藤恭子，武本真治，平 雅之，鬼原英道，西郷 慶悦，近藤尚知.
  • Organizer: 第48回日本口腔インプラント学会
• [Presentation] Mesenchymal stem cells educate undifferentiated monocyte/macrophages to the M2 macrophages in cell-cell adhesion-dependent and independent ways (2017)
  • Author(s): Takizawa N, Okubo N, Kamo M, Chosa N, Mikami T, Suzuki K, Yokota S, Ibi M, Ohtsuka M, Taira M, Sasaki D, Yaegashi T, Ishisaki A, Kyakumoto S
  • Organizer: 第65回国際歯科研究学会日本部会（JADR）学術大会
  • Int'l Joint Research
• [Presentation] 架橋型ヒアルロン酸・ナノアパタイト・BMPを用いた注入式骨補填材の試作 (2016)
  • Author(s): 池田功司，平 雅之，畠山 航，高藤恭子，近藤尚知．
  • Organizer: 第46回日本口腔インプラント学会
  • Place of Presentation: 名古屋市
  • Year and Date: 2016-09-12