miR-140-5p regulates the odontoblastic differentiation of dental pulp stem cells via the Wnt1/β-catenin signaling pathway

Abstract

Background MicroRNAs (miRNAs) play a key role in regulating cell differentiation. In the present study, we aimed to explore the role of miR-140-5p in odontoblastic differentiation of dental pulp stem cells (DPSCs). Methods DPSCs from normal human impacted third molars were isolated and cultured. After overexpression or silencing of miR-140-5p in DPSCs, activity, proliferation, and odontoblastic differentiation of DPSCs were evaluated. The possible target gene of miR-140-5p was verified by luciferase reporter gene assay. Using gene transfection technology, RT-CPR, and Western blot to confirm miR-140-5p regulates the odontoblastic differentiation of DPSCs through Wnt1/β-catenin signaling. Results We found the expression of miR-140-5p decreased in the differentiated DPSCs for odontoblastic cells, and at the same time, the expressions of Wnt1 and β-catenin increased. Wnt1 was the target gene of miR-140-5p which was confirmed by luciferase reporter gene system. miR-140-5p overexpression suppressed the expression of Wnt1. miR-140-5p inhibitor could promote the odontoblastic differentiation of DPSCs. miR-140-5p mimic could weaken the odontoblastic differentiation of DPSCs, which could be reversed by the overexpression of Wnt1. Conclusion Our data demonstrated that miR-140-5p regulates the odontoblastic differentiation of DPSCs via targeting Wnt1/β-catenin signaling. Therefore, miR-140-5p might be a molecular target to regulate the odontoblastic differentiation for the therapeutic agents in dental medicine. Electronic supplementary material The online version of this article (10.1186/s13287-019-1344-4) contains supplementary material, which is available to authorized users.

Isoflurane-induced expression of miR-140-5p aggravates neurotoxicity in diabetic rats by targeting SNX12

“…In our study, knockdown of miR-140-5p decreased the expression of Cleaved Caspase-3 and increased the expression of Bcl-2 to inhibit hippocampal neuronal apoptosis in diabetic rats with isoflurane anesthesia. Wnt1 was identified as a target of miR-140-5p in neonatal rats for cerebral protection (Han et al, 2018) or in dental pulp stem cells for odontoblastic differentiation (Lu et al, 2019). In the present study, SNX12 was identified as a new target of miR-140-5p.…”

“…However, whether miRNAs are associated with isoflurane-related cognitive dysregulation in diabetes has not been reported yet. MiR-140-5p was identified as a tumor suppressor in gastric cancer (Fang et al, 2017), and regulates odontoblastic differentiation (Lu et al, 2019). More recently, miR-140-5p was shown to protect against hypoxic-ischaemic brain damage via promotion of learning and memory abilities (Han et al, 2018).…”

Epigenetic Regulation of Dental Pulp Stem Cell Fate

“…Some other miRNAs are also associated with the osteo/odontogenic differentiation of DPSCs. miR-140-5p is decreased when DPSCs are induced into odontoblasts, and miR-140-5p mimic can impair the odontogenic differentiation through suppressing the Wnt1/ β -catenin signaling pathway by targeting Wnt1 [ 153 ]. Insulin-like growth factor 1 has been proved to induce the proliferation and osteo/odontogenic differentiation of DPSCs via activation of the P38 MAPK and JNK pathways.…”

The Circular RNA circRNA124534 Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Modulation of the miR-496/β-Catenin Pathway

“…CyclinDl, Runx2, and other target genes can regulate physiological activities, such as cell proliferation and bone differentiation (Kleber and Sommer, 2004;Wilusz and Majka, 2008). β-catenin has been shown to regulate osteogenic differentiation of DPSCs (Lu et al, 2019). In the current study, we showed that miR-496 interacts with the 3 UTR of β-catenin and suppresses β-catenin activity at the post-transcriptional level.…”