METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation
Mesenchymal stem cells (MSCs) have been considered a potential method for the regeneration of tooth and maxillofacial bone defects based on the multidirectional differentiation characteristics of MSCs. miRNAs have been found to play a key role in the differentiation of MSCs. However, its effectivene...
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Format: | Article |
Language: | English |
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Wiley
2023-01-01
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Series: | Stem Cells International |
Online Access: | http://dx.doi.org/10.1155/2023/8992284 |
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author | Xiao Han Guoyue Li Haoqing Yang Chen Zhang Yangyang Cao Ning Wang Lihua Ge Zhipeng Fan |
author_facet | Xiao Han Guoyue Li Haoqing Yang Chen Zhang Yangyang Cao Ning Wang Lihua Ge Zhipeng Fan |
author_sort | Xiao Han |
collection | DOAJ |
description | Mesenchymal stem cells (MSCs) have been considered a potential method for the regeneration of tooth and maxillofacial bone defects based on the multidirectional differentiation characteristics of MSCs. miRNAs have been found to play a key role in the differentiation of MSCs. However, its effectiveness still needs to be improved, and its internal mechanism is still unclear. In the present study, our data discovered that the knockdown of miR-196b-5p promoted alkaline phosphatase (ALP) activity assay, mineralization in vitro, and expressions of osteo/odontogenic differentiation markers DSPP and OCN and enhanced in vivo osteo/odontogenic differentiation of stem cells of the apical papilla (SCAPs). Mechanistically, the results indicated that METTL3-dependent N6-methyladenosine (m6A) methylation inhibited miR-196b-5p maturation by the microprocessor protein DGCR8. Moreover, miR-196b-5p indirectly negatively regulates METTL3 in SCAPs. Then, METTL3 was found to strengthen the ALP activity assay, mineralization, and expressions of osteo/dentinogenic differentiation markers. Taken together, our findings highlight the critical roles of the METTL3-miR-196b-5p signaling axis in an m6A-dependent manner in osteo/odontogenic differentiation of SCAPs, identifying some potential targets for tooth and maxillofacial bone defects. |
format | Article |
id | doaj-art-4015ba2775ad4c64b9c0fab7ebb43ba0 |
institution | Kabale University |
issn | 1687-9678 |
language | English |
publishDate | 2023-01-01 |
publisher | Wiley |
record_format | Article |
series | Stem Cells International |
spelling | doaj-art-4015ba2775ad4c64b9c0fab7ebb43ba02025-02-03T06:45:41ZengWileyStem Cells International1687-96782023-01-01202310.1155/2023/8992284METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p MaturationXiao Han0Guoyue Li1Haoqing Yang2Chen Zhang3Yangyang Cao4Ning Wang5Lihua Ge6Zhipeng Fan7Beijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Key Laboratory of Tooth Regeneration and Function ReconstructionBeijing Key Laboratory of Tooth Regeneration and Function ReconstructionMesenchymal stem cells (MSCs) have been considered a potential method for the regeneration of tooth and maxillofacial bone defects based on the multidirectional differentiation characteristics of MSCs. miRNAs have been found to play a key role in the differentiation of MSCs. However, its effectiveness still needs to be improved, and its internal mechanism is still unclear. In the present study, our data discovered that the knockdown of miR-196b-5p promoted alkaline phosphatase (ALP) activity assay, mineralization in vitro, and expressions of osteo/odontogenic differentiation markers DSPP and OCN and enhanced in vivo osteo/odontogenic differentiation of stem cells of the apical papilla (SCAPs). Mechanistically, the results indicated that METTL3-dependent N6-methyladenosine (m6A) methylation inhibited miR-196b-5p maturation by the microprocessor protein DGCR8. Moreover, miR-196b-5p indirectly negatively regulates METTL3 in SCAPs. Then, METTL3 was found to strengthen the ALP activity assay, mineralization, and expressions of osteo/dentinogenic differentiation markers. Taken together, our findings highlight the critical roles of the METTL3-miR-196b-5p signaling axis in an m6A-dependent manner in osteo/odontogenic differentiation of SCAPs, identifying some potential targets for tooth and maxillofacial bone defects.http://dx.doi.org/10.1155/2023/8992284 |
spellingShingle | Xiao Han Guoyue Li Haoqing Yang Chen Zhang Yangyang Cao Ning Wang Lihua Ge Zhipeng Fan METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation Stem Cells International |
title | METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation |
title_full | METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation |
title_fullStr | METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation |
title_full_unstemmed | METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation |
title_short | METTL3 Promotes Osteo/Odontogenic Differentiation of Stem Cells by Inhibiting miR-196b-5p Maturation |
title_sort | mettl3 promotes osteo odontogenic differentiation of stem cells by inhibiting mir 196b 5p maturation |
url | http://dx.doi.org/10.1155/2023/8992284 |
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