Inhibition of ATG7 promotes orthodontic tooth movement by regulating the RANKL/OPG ratio under compression force.

Abstract

Objective: Autophagy serves as a protective mechanism in response to mechanical stress during OTM. However, the role of ATG7, a key regulatory gene in autophagy, in modulating periodontium remodeling during OTM remains unclear. This study aims to investigate the potential modulation of periodontium remodeling by ATG7 under compression force.

Materials and methods: HPDLSCs and a rat OTM model were used as in vitro and in vivo systems to study the effect of compressive stress on autophagy and osteoclast-related markers. To investigate the role of ATG7, hPDLSCs with ATG7 knockdown and ATG7^+/- rats were used in this study.

Results: Compression force activates autophagy and increases the RANKL/OPG ratio. ATG7 knockdown significantly suppresses autophagy in hPDLSCs, while the RANKL/OPG ratio is markedly elevated. Under compression stress, hPDLSCs-siATG7 markedly enhanced RANKL/OPG expression. In the rat OTM model, autophagy was significantly activated in the periodontium on the compression side. Compared to wild-type SD rats, ATG7^+/- rats exhibit reduced autophagy-related protein expression, an increased RANKL/OPG ratio, and accelerated tooth movement.

Conclusions: Under compression force, inhibition of ATG7 expression significantly increases the RANKL/OPG ratio both in vivo and in vitro, which is accompanied by an increased rate of orthodontic tooth movement.