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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-93256-y |
| _version_ | 1818843485552246784 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T04:58:37Z |
| format | Article |
| id | doaj.art-b69b2500ef85490687eba3c4e049a2f7 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:58:37Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b69b2500ef85490687eba3c4e049a2f72022-12-21T20:35:10ZengNature PortfolioScientific Reports2045-23222021-07-011111910.1038/s41598-021-93256-yLocal application of Usag-1 siRNA can promote tooth regeneration in Runx2-deficient miceSayaka Mishima0Katsu Takahashi1Honoka Kiso2Akiko Murashima-Suginami3Yoshihito Tokita4Jun-Ichiro Jo5Ryuji Uozumi6Yukiko Nambu7Boyen Huang8Hidemitsu Harada9Toshihisa Komori10Manabu Sugai11Yasuhiko Tabata12Kazuhisa Bessho13Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto UniversityDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto UniversityDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto UniversityDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto UniversityDepartment of Perinatology, Institute for Developmental Research, Aichi Human Service CenterDepartment of Biomaterials, Institute for Frontier Medical Sciences, Kyoto UniversityDepartment of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto UniversityDepartment of Molecular Genetics, Division of Medicine, Faculty of Medical Sciences, University of FukuiDepartment of Primary Dental Care, University of Minnesota School of DentistryDepartment of Anatomy, Division of Developmental Biology and Regenerative Medicine1-1-1, Iwate Medical UniversityBasic and Translational Research Center for Hard Tissue Disease, Nagasaki University Graduate School of Biomedical SciencesDepartment of Molecular Genetics, Division of Medicine, Faculty of Medical Sciences, University of FukuiDepartment of Biomaterials, Institute for Frontier Medical Sciences, Kyoto UniversityDepartment of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto UniversityAbstract 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.https://doi.org/10.1038/s41598-021-93256-y |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-93256-y |
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