miR-223-3p Mitigates Mitochondrial Dysfunction and Cementoblast Apoptosis in Orthodontic Root Resorption via FoxO3.

Abstract

Aim: The aim of this study was to elucidate the roles of miR-223-3p in orthodontically induced inflammatory root resorption (OIIRR).

Methods: We used high-throughput miRNA sequencing and transcriptome sequencing to analyze the differentially expressed miRNAs and mRNAs in OCCM-30 cells under hypoxia. Real-time quantitative PCR (RT-qPCR) and Western blotting were used to assess the expression of genes and proteins related to apoptosis, oxidative stress, and mitochondrial dysfunction. Fluorescence staining was employed to detect changes in cellular ROS (reactive oxygen species), MMP (mitochondrial membrane potential), and mtROS (mitochondrial ROS) expression.

Results: We found that miR-223-3p targeted FoxO3 to regulate apoptosis in cementoblasts under hypoxic conditions. Moreover, hypoxia-induced FoxO3 increased oxidative stress and induced mitochondrial dysfunction in cementoblasts, resulting in cell apoptosis. Administration of the ROS inhibitor NAC (N-acetyl cysteine) effectively reversed FoxO3-induced oxidative stress and mitochondrial dysfunction, thereby rescuing cell apoptosis.

Conclusions: miR-223-3p targets FoxO3 and regulates the apoptosis of cementoblasts by improving oxidative stress and mitochondrial dysfunction. These findings may offer new insights into the mechanism of OIIRR.