Journal Article

Inhibition of miR-615-3p enhances dentinogenesis in scaps via PVT1-mediated mitochondrial regulation

Han, Xiao, Huang, Yishu, Yuan, Fengning, Song, Jiaxin, Yang, Haoqing, Fan, Zhipeng

2025

Overview

Background Mesenchymal stem cells (MSCs) are critical for dental tissue regeneration, yet their differentiation potential is tightly regulated by microRNAs (miRNAs). This study aimed to investigate the role of miR-615-3p in regulating odontogenic differentiation in stem cells from the apical papilla (SCAPs), offering insights into potential applications for enhancing dental tissue regeneration and repair. Methods Quantitative PCR (qPCR), Western blot analysis, alkaline phosphatase (ALP) activity assay, and Alizarin Red staining (ARS) were performed to assess odontogenic differentiation following miR-615-3p modulation in SCAPs. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels, membrane potential, and respiratory activity. In vivo, SCAPs with miR-615-3p modulation were transplanted into rabbit extraction sockets to examine dentin-like tissue formation. Results miR-615-3p was significantly downregulated in SCAPs compared to umbilical cord mesenchymal stem cells (WJCMSCs) and further decreased during mineralization induction, suggesting its negative regulatory role in odontogenic differentiation. Inhibition of miR-615-3p enhanced ALP activity, mineralization, and odontogenic marker expression both in vitro and in vivo. Proteomic analysis revealed that miR-615-3p inhibition improved mitochondrial function by reducing ROS levels and increasing mitochondrial function. Further Competing Endogenous RNA Sequencing(ceRNA-seq) analysis identified PVT1 as a downstream target of miR-615-3p. PVT1 overexpression promoted odontogenic differentiation and mitochondrial homeostasis, while its knockdown impaired these processes. Collectively, the miR-615-3p/PVT1 axis emerged as a critical regulator of dentinogenesis through mitochondrial modulation. Conclusions Inhibiting miR-615-3p fosters dentinogenesis through PVT1-mediated mitochondrial regulation in SCAPs. These findings highlight the miR-615-3p/PVT1 axis as a promising target for enhancing dentin tissue engineering applications.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Alkaline phosphatase / Antibodies / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Care and treatment / Cell Biology / Cell culture / Cell differentiation / Cellular control mechanisms / Dental research / Dentin / Dentinogenesis / Gene expression / Health aspects / Homeostasis / Jaw / Life Sciences / MCSs / Medical research / Membrane potential / Mesenchymal stem cells / Metabolism / MicroRNA / MicroRNAs / Mineralization / miR-615-3p / miRNA / Mitochondria / Mitochondrial function / Odontogenesis / Odontogenic differentiation / Phosphorylation / Physiological aspects / Proteins / Proteomics / PVT1 / Reactive oxygen species / Regeneration (Biology) / Regenerative Medicine/Tissue Engineering / Roles / Stem Cells / Tissue engineering / Tooth diseases / Transplants & implants / Umbilical cord