Author:
Mishima Sayaka,Takahashi Katsu,Kiso Honoka,Murashima-Suginami Akiko,Tokita Yoshihito,Jo Jun-Ichiro,Uozumi Ryuji,Nambu Yukiko,Huang Boyen,Harada Hidemitsu,Komori Toshihisa,Sugai Manabu,Tabata Yasuhiko,Bessho Kazuhisa
Abstract
AbstractRunt-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.
Funder
Japan Agency for Medical Research and Development
Publisher
Springer Science and Business Media LLC
Reference30 articles.
1. Ardakani, F. E., Sheikhha, M. & Ahmadi, H. Prevalence of dental developmental anomalies: A radiographic study. Commun. Dent. Health 24, 140–144 (2007).
2. Machida, J. et al. Genetic epidemiology of tooth agenesis in Japan: a population- and family-based study. Clin. Genet. 88, 167–171 (2015).
3. Machida, J. et al. WNT10A variants isolated from Japanese patients with congenital tooth agenesis. Hum. Genome Var. 4, 17047. https://doi.org/10.1038/hgv.2017.47 (2017).
4. Chhabra, N., Goswami, M. & Chhabra, A. Genetic basis of dental agenesis–molecular genetics patterning clinical dentistry. Med. Oral Patol. Oral Cir. Bucal. 19, e112–e119 (2014).
5. Callea, M., Fattori, F., Yavuz, I. & Bertini, E. A new phenotypic variant in cleidocranial dysplasia (CCD) associated with mutation c.391C>T of the RUNX2 gene. BMJ Case Rep. https://doi.org/10.1136/bcr-12-2011-5422 (2012).
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