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

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 k...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b69b2500ef85490687eba3c4e049a2f7
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spelling	oai:doaj.org-article:b69b2500ef85490687eba3c4e049a2f72021-12-02T14:33:51ZLocal application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice10.1038/s41598-021-93256-y2045-2322https://doaj.org/article/b69b2500ef85490687eba3c4e049a2f72021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93256-yhttps://doaj.org/toc/2045-2322Abstract 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.Sayaka MishimaKatsu TakahashiHonoka KisoAkiko Murashima-SuginamiYoshihito TokitaJun-Ichiro JoRyuji UozumiYukiko NambuBoyen HuangHidemitsu HaradaToshihisa KomoriManabu SugaiYasuhiko TabataKazuhisa BesshoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice
description	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.
format	article
author	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
author_facet	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
author_sort	Sayaka Mishima
title	Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice
title_short	Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice
title_full	Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice
title_fullStr	Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice
title_full_unstemmed	Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice
title_sort	local application of usag-1 sirna can promote tooth regeneration in runx2-deficient mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b69b2500ef85490687eba3c4e049a2f7
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Local application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient mice

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