Molecular Mechanisms Of Chronotherapy In Orthodontic Tooth Movement

Orthodontic treatment faces challenges of prolonged duration and complications. This study investigates circadian mechanisms underlying force application timing to accelerate tooth movement (OTM) while minimizing adverse effects. Standardized circadian rat models underwent transcriptomic profiling of periodontal ligaments (9 Zeitgeber timepoints). OTM forces were applied at ZT0/6/12/18 for 14 days. Micro-CT, H&E/TRAP staining quantified tooth movement and root/bone resorption. qRT-PCR/Western blot analyzed mechanosensitive molecule rhythms. 1) Physiological periodontal activities exhibited circadian rhythms, with actin cytoskeleton regulation peaking during early active phase. 2) Force timing significantly influenced OTM efficiency: early active phase application achieved 38% faster movement versus other intervals (Micro-CT, p<0.01), without root resorption complications (H&E/TRAP confirmation). Mechanosensitive molecules (e.g., FAK, YAP) showed synchronized circadian expression patterns correlating with optimal force responsiveness. Transcriptomics identified 214 rhythmically expressed genes in cytoskeletal organization and osteoclast regulation pathways. Circadian-force synchronization capitalizes on endogenous mechanosensitive rhythms to enhance OTM efficiency and safety. Early active phase application, aligned with peak cytoskeletal dynamics, represents a novel chronotherapeutic strategy for optimized orthodontics, potentially reducing treatment duration by 30-40% while preventing iatrogenic damage.