A Chemically Defined Culture for Tooth Reconstitution
Abstract It is known for decades that dental epithelium and mesenchyme can reconstitute and regenerate a functional tooth. However, the mechanism of tooth reconstitution remains largely unknown due to the lack of an efficient in vitro model. Here, a chemically defined culture system is established t...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202404345 |
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| author | Ziwei Zhang Hong Hu Zhiheng Xu Ce Shan Hanyi Chen Kun Xie Kun Wang Yifu Wang Qing Zhu Yike Yin Haoyang Cai Yunqiu Zhang Zhonghan Li |
| author_facet | Ziwei Zhang Hong Hu Zhiheng Xu Ce Shan Hanyi Chen Kun Xie Kun Wang Yifu Wang Qing Zhu Yike Yin Haoyang Cai Yunqiu Zhang Zhonghan Li |
| author_sort | Ziwei Zhang |
| collection | DOAJ |
| description | Abstract It is known for decades that dental epithelium and mesenchyme can reconstitute and regenerate a functional tooth. However, the mechanism of tooth reconstitution remains largely unknown due to the lack of an efficient in vitro model. Here, a chemically defined culture system is established that supports tooth reconstitution, further development with normal anatomy, and prompt response to chemical interference in key developmental signaling pathways, termed as toothoids. By using such a system, it is discovered that, during reconstitution, instead of resetting the developmental clock, dental cells reorganized and restarted from the respective developmental stage where they are originally isolated. Moreover, co‐stimulation of Activin A and Hedgehog/Smoothened agonist (SAG) sustained the initial induction of tooth fate from the first branchial arch, which would be otherwise quickly lost in culture. Furthermore, activation of Bone Morphogenetic Protein (BMP) signaling triggered efficient enamel formation in the late‐stage toothoids, without affecting the normal development of ameloblasts. Together, these data highlight the toothoid culture as a powerful tool to dissect the molecular mechanisms of tooth reconstitution and regeneration. |
| format | Article |
| id | doaj-art-d1c9eeeb3fc54aeba60de40c16122e0c |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-d1c9eeeb3fc54aeba60de40c16122e0c2025-01-20T13:04:18ZengWileyAdvanced Science2198-38442025-01-01123n/an/a10.1002/advs.202404345A Chemically Defined Culture for Tooth ReconstitutionZiwei Zhang0Hong Hu1Zhiheng Xu2Ce Shan3Hanyi Chen4Kun Xie5Kun Wang6Yifu Wang7Qing Zhu8Yike Yin9Haoyang Cai10Yunqiu Zhang11Zhonghan Li12Center of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaCenter of Growth Metabolism and Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province College of Life Sciences Sichuan University 24 South Section 1, 1st Ring Road Chengdu 610065 ChinaAbstract It is known for decades that dental epithelium and mesenchyme can reconstitute and regenerate a functional tooth. However, the mechanism of tooth reconstitution remains largely unknown due to the lack of an efficient in vitro model. Here, a chemically defined culture system is established that supports tooth reconstitution, further development with normal anatomy, and prompt response to chemical interference in key developmental signaling pathways, termed as toothoids. By using such a system, it is discovered that, during reconstitution, instead of resetting the developmental clock, dental cells reorganized and restarted from the respective developmental stage where they are originally isolated. Moreover, co‐stimulation of Activin A and Hedgehog/Smoothened agonist (SAG) sustained the initial induction of tooth fate from the first branchial arch, which would be otherwise quickly lost in culture. Furthermore, activation of Bone Morphogenetic Protein (BMP) signaling triggered efficient enamel formation in the late‐stage toothoids, without affecting the normal development of ameloblasts. Together, these data highlight the toothoid culture as a powerful tool to dissect the molecular mechanisms of tooth reconstitution and regeneration.https://doi.org/10.1002/advs.202404345enamel inductionserum‐freetooth reconstitutiontoothoid |
| spellingShingle | Ziwei Zhang Hong Hu Zhiheng Xu Ce Shan Hanyi Chen Kun Xie Kun Wang Yifu Wang Qing Zhu Yike Yin Haoyang Cai Yunqiu Zhang Zhonghan Li A Chemically Defined Culture for Tooth Reconstitution Advanced Science enamel induction serum‐free tooth reconstitution toothoid |
| title | A Chemically Defined Culture for Tooth Reconstitution |
| title_full | A Chemically Defined Culture for Tooth Reconstitution |
| title_fullStr | A Chemically Defined Culture for Tooth Reconstitution |
| title_full_unstemmed | A Chemically Defined Culture for Tooth Reconstitution |
| title_short | A Chemically Defined Culture for Tooth Reconstitution |
| title_sort | chemically defined culture for tooth reconstitution |
| topic | enamel induction serum‐free tooth reconstitution toothoid |
| url | https://doi.org/10.1002/advs.202404345 |
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