A new strategy of bone metabolism activation to promote tooth movement: Nanoparticle-based DDS approach

• Project/Area Number: 15K11342
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ishida Yuji 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (00516297)
• Co-Investigator(Kenkyū-buntansha): 鈴木 淳一 東京大学, 医学部附属病院, 特任准教授 (90313858) ; 岩崎 剣吾 大阪歯科大学, 歯学部, 講師 (40401351) ; 細道 純 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (00420258)
• Research Collaborator: YAMAGUCHI Hiroyuki ; HATANO Kasumi ; LI Kai ; NARUBHORN Ongprakobkul
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: SDF-1 / 矯正歯科 / 歯の移動 / AMD3100 / 矯正的歯の移動 / 骨代謝 / 移動促進 / ピエゾサージェリー / 組織学 / 生化学

Outline of Final Research Achievements

We investigated the role SDF-1 during orthodontic tooth movement using animal model. SDF-1 expression was recognized in the compression side of periodontal ligament during orthodontic tooth movement. In addition, continuous systemic administration of AMD 3100, which is an SDF-1 / CXCR4 signal inhibitor, results in continuous suppression of tooth movement, but the suppression effect is dependent on elapsed time, and it became clear that SDF-1, Cathepsin K, Runx2 expression decreases under administration of AMD 3100 during orthodontic tooth movement. This effect was also observed when administered locally. From the above results, it was revealed that SDF-1 / CXCR4 signal plays a major role in its early stage during corrective tooth movement.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は、これまで知られていなかった矯正力による歯の移動時の歯槽骨代謝において、ケモカインであるＳＤＦ－１が歯の移動の初期段階において発現されること、また骨折治癒などにおける関与が注目されるＳＤＦ－１／ＣＸＣＲ４シグナルの新たな役割が明らかとなり、ＳＤＦ－１／ＣＸＣＲ４シグナル制御による歯槽骨代謝活性制御法を発展させ、安全かつ効率的な歯の移動を促進する新規治療法開発の基盤研究となることが期待される。

Research Products

• [Journal Article] The chemokine receptor type 4 antagonist, AMD3100, interrupts experimental tooth movement in rats (2018)
  • Author(s): Hatano Kasumi、Ishida Yuji、Yamaguchi Hiroyuki、Hosomichi Jun、Suzuki Jun-ichi、Usumi-Fujita Risa、Shimizu Yasuhiro、Shibutani Naoki、Kaneko Sawa、Ono Takashi
  • Journal Title: Archives of Oral Biology Volume: 86 Pages: 35-39
  • DOI: 10.1016/j.archoralbio.2017.11.003
  • Peer Reviewed
• [Journal Article] A new approach to transfect NF-κB decoy oligodeoxynucleotides into the periodontal tissue using the ultrasound-microbubble method. (2017)
  • Author(s): Yamaguchi Hiroyuki, Ishida Yuji, Hosomichi Jun, et al
  • Journal Title: International Journal of Oral Science Volume: 印刷中 Issue: 2 Pages: 80-86
  • DOI: 10.1038/ijos.2017.10
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Effects of AMD3100 on orthodontic tooth movement after local/systemic administration (2018)
  • Author(s): Narubhorn Ongprakobkul, Yuji Ishida, Kasumi Hatano -Sato, Kai Li, Sirima Petdachai, Jun Hosomichi, Korapin Mahatumarat, Takashi Ono
  • Organizer: 2019 IADR/AADR/CADR General Session-Poster Presentation
  • Int'l Joint Research
• [Presentation] SDF-1/CXCR4歯グラぬ阻害はラット臼歯の矯正的移動を遅延する (2016)
  • Author(s): 畑野香澄、石田雄之、山口博之、他11名
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: アスティとくしま（徳島県徳島市、日本）
  • Year and Date: 2016-11-07
• [Presentation] 超音波マイクロバブル法を応用した歯周組織に対する新規NF-ｋBデコイ導入法の開発 (2016)
  • Author(s): 山口博之、石田雄之、細道純、他12名
  • Organizer: 第75回日本矯正歯科学会大会
  • Place of Presentation: アスティとくしま（徳島県徳島市、日本）
  • Year and Date: 2016-11-07