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...

Full description

Saved in:
Bibliographic Details
Main Authors: Xiao Han, Guoyue Li, Haoqing Yang, Chen Zhang, Yangyang Cao, Ning Wang, Lihua Ge, Zhipeng Fan
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2023/8992284
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832547141994676224
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
work_keys_str_mv AT xiaohan mettl3promotesosteoodontogenicdifferentiationofstemcellsbyinhibitingmir196b5pmaturation
AT guoyueli mettl3promotesosteoodontogenicdifferentiationofstemcellsbyinhibitingmir196b5pmaturation
AT haoqingyang mettl3promotesosteoodontogenicdifferentiationofstemcellsbyinhibitingmir196b5pmaturation
AT chenzhang mettl3promotesosteoodontogenicdifferentiationofstemcellsbyinhibitingmir196b5pmaturation
AT yangyangcao mettl3promotesosteoodontogenicdifferentiationofstemcellsbyinhibitingmir196b5pmaturation
AT ningwang mettl3promotesosteoodontogenicdifferentiationofstemcellsbyinhibitingmir196b5pmaturation
AT lihuage mettl3promotesosteoodontogenicdifferentiationofstemcellsbyinhibitingmir196b5pmaturation
AT zhipengfan mettl3promotesosteoodontogenicdifferentiationofstemcellsbyinhibitingmir196b5pmaturation