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3D-Printed β-Tricalcium Phosphate Scaffolds Promote Osteogenic Differentiation of Bone Marrow-Deprived Mesenchymal Stem Cells in an N6-methyladenosine- Dependent Manner

Authors :
Xin, Jiao
Xin, Sun
Wentao, Li
Wenxiang, Chu
Yuxin, Zhang
Yiming, Li
Zengguang, Wang
Xianhao, Zhou
Jie, Ma
Chen, Xu
Kerong, Dai
Jinwu, Wang
Yaokai, Gan
Source :
International Journal of Bioprinting. 8
Publication Year :
2022
Publisher :
Whioce Publishing Pte Ltd, 2022.

Abstract

Bone defect is a serious orthopedic disease which has been studied for a long time. Alternative degradable biomaterials are required for bone repairing and regeneration to address the limitation of autogenous bone. β-tricalcium phosphate (β-TCP) is an alternative material with good cytocompatibility and has been used in bone defect treatment. However, whether β-TCP contributes to osteogenesis of bone marrow stem cells (BMSCs) through N6-methyladenosine (m6A) modification remains unknown. To address this issue, we verified the effects of β-TCP on osteogenesis of BMSCs. We also studied the expression of m6A-related enzymes in BMSCs after β-TCP treatment. Furthermore, the m6A level and stability of Runt-related transcription factor 2 (RUNX2) mRNA were investigated after β-TCP treatment. Finally, rat calvarial defect models were performed to detect expression level of osteogenic factors and m6A-related enzymes after the stimulation of three-dimension (3D)-printed β-TCP scaffolds. We found that β-TCP showed good biocompatibility and was osteoinductive. Meanwhile, methyltransferase-like 3 (METTL3) increased, causing the elevation of m6A level of RUNX2, results in stabler RUNX2 mRNA level. At last, based on the animal experiments, we demonstrated that the increase of RUNX2 and METTL3 levels was induced by β-TCP. These findings suggest that METTL3 increases the m6A level of RUNX2 mRNA after β-TCP induction, contributing to its stability, and the results in vivo also confirmed the osteogenic and bone-repair properties of β-TCP.

Details

ISSN :
24248002 and 24247723
Volume :
8
Database :
OpenAIRE
Journal :
International Journal of Bioprinting
Accession number :
edsair.doi.dedup.....7da6aa7f7c4f66bd26ab241426166619
Full Text :
https://doi.org/10.18063/ijb.v8i2.544