1. Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice
- Author
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Sayaka Mishima, Jun-ichiro Jo, Hidemitsu Harada, Yasuhiko Tabata, Manabu Sugai, Kazuhisa Bessho, Boyen Huang, Ryuji Uozumi, Yoshihito Tokita, Honoka Kiso, Yukiko Nambu, Katsu Takahashi, Akiko Murashima-Suginami, and Toshihisa Komori
- Subjects
Small interfering RNA ,Molecular biology ,Science ,Core Binding Factor Alpha 1 Subunit ,Diseases ,Mandible ,Biology ,Article ,Mice ,Renal capsule ,stomatognathic system ,Developmental biology ,medicine ,Animals ,Regeneration ,RNA, Small Interfering ,Transcription factor ,Adaptor Proteins, Signal Transducing ,Mice, Knockout ,Gene knockdown ,Multidisciplinary ,Tooth regeneration ,Molecular medicine ,Drug discovery ,Gene Expression Regulation, Developmental ,medicine.disease ,Cell biology ,RUNX2 ,Transplantation ,Mice, Inbred C57BL ,stomatognathic diseases ,medicine.anatomical_structure ,Agenesis ,Medicine ,Odontogenesis ,RNA Interference ,Tooth - 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.
- Published
- 2021