Scientific Reports (Jul 2021)

Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice

  • Sayaka Mishima,
  • Katsu Takahashi,
  • Honoka Kiso,
  • Akiko Murashima-Suginami,
  • Yoshihito Tokita,
  • Jun-Ichiro Jo,
  • Ryuji Uozumi,
  • Yukiko Nambu,
  • Boyen Huang,
  • Hidemitsu Harada,
  • Toshihisa Komori,
  • Manabu Sugai,
  • Yasuhiko Tabata,
  • Kazuhisa Bessho

DOI
https://doi.org/10.1038/s41598-021-93256-y
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 9

Abstract

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Abstract Runt-related transcription factor 2 (Runx2)-deficient mice can be used to model congenital tooth agenesis in humans. Conversely, uterine sensitization-associated gene-1 (Usag-1)-deficient mice exhibit supernumerary tooth formation. Arrested tooth formation can be restored by crossing both knockout-mouse strains; however, it remains unclear whether topical inhibition of Usag-1 expression can enable the recovery of tooth formation in Runx2-deficient mice. Here, we tested whether inhibiting the topical expression of Usag-1 can reverse arrested tooth formation after Runx2 abrogation. The results showed that local application of Usag-1 Stealth small interfering RNA (siRNA) promoted tooth development following Runx2 siRNA-induced agenesis. Additionally, renal capsule transplantation of siRNA-loaded cationized, gelatin-treated mouse mandibles confirmed that cationized gelatin can serve as an effective drug-delivery system. We then performed renal capsule transplantation of wild-type and Runx2-knockout (KO) mouse mandibles, treated with Usag-1 siRNA, revealing that hindered tooth formation was rescued by Usag-1 knockdown. Furthermore, topically applied Usag-1 siRNA partially rescued arrested tooth development in Runx2-KO mice, demonstrating its potential for regenerating teeth in Runx2-deficient mice. Our findings have implications for developing topical treatments for congenital tooth agenesis.