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

Sci Rep. 2021 Jul 1;11(1):13674. doi: 10.1038/s41598-021-93256-y.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Core Binding Factor Alpha 1 Subunit / genetics*
  • Gene Expression Regulation, Developmental
  • Mandible / transplantation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Odontogenesis*
  • RNA Interference
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / pharmacology
  • Regeneration
  • Tooth / growth & development*
  • Tooth / physiology


  • Adaptor Proteins, Signal Transducing
  • Core Binding Factor Alpha 1 Subunit
  • RNA, Small Interfering
  • Runx2 protein, mouse
  • Sostdc1 protein, mouse