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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number13674
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Jul 1 2021

Bibliographical note

Funding Information:
This study was supported by Grants-in-Aid for Scientific Research [Grant Nos. (C):25463081 and 17K118323], the Japan Agency for Medical Research and Development [Grant Nos. JP17nk0101334 and JP 20ek0109397] and the Fourth GAP Fund and Incubation Program (Kyoto University).

Publisher Copyright:
© 2021, The Author(s).

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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