Epigenetic Blueprints in Periodontal Ligament Cells during Orthodontic Tooth Movement: Unlocking Molecular Secrets for Precision-Guided Therapy in Modern Orthodontics

Abstract

Background: Orthodontic tooth movement involves complex cellular responses influenced by mechanical forces. This study investigates the impact of mechanical forces on periodontal ligament (PDL) fibroblasts, focusing on epigenetic modifications and gene expression related to bone remodeling.

Materials and Methods: Fifteen human premolars extracted for clinical reasons were utilized. PDL fibroblasts were cultured and subjected to mechanical forces using a custom-designed system, applying compressive and tensile forces of 1g and 2g for durations of 12, 24, and 48 hours. Epigenetic changes were assessed through DNA methylation analysis, histone modification studies (H3K27ac and H3K4me3), and non-coding RNA expression (miR-21 and miR-146a). Gene expression levels of RANKL, OPG, and RUNX2 were measured using quantitative PCR. Statistical analyses were performed using paired t-tests and ANOVA.

Results: Cell viability remained high across all conditions, indicating that mechanical forces did not adversely affect cell survival. Increased methylation of the RANKL gene and elevated levels of H3K27ac and H3K4me3 modifications were observed with applied forces, particularly at 48 hours and higher force levels. miR-21 expression significantly increased, while miR-146a showed a gradual rise over time. RANKL expression decreased with mechanical forces, whereas OPG expression remained relatively stable.

Conclusion: Mechanical forces applied to PDL fibroblasts lead to significant epigenetic and gene expression changes, with increased RANKL gene methylation, histone acetylation, and altered miRNA expression. These findings enhance understanding of the molecular mechanisms behind orthodontic tooth movement and suggest potential targets for precision orthodontic therapies.