Effects Of Atg7 On Pdlscs Differentiation Under Compressive Stress

Autophagy is a critical biological process in orthodontic tooth movement (OTM), yet its role in modulating osteogenic differentiation and osteoclastogenesis under compressive stress remains unclear. This study aims to investigate the effects of ATG7, a key autophagy gene, on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and its regulatory role in osteoclast differentiation under compressive stress. PDLSCs were identified based on multidirectional differentiation potential, colony formation, and flow cytometry analysis of surface markers. A compressive force of 2 g/cm² was applied to PDLSCs, and Western blot (WB) and RT-qPCR were used to determine the optimal time duration for autophagy and differentiation responses. Subsequently, PDLSCs were transfected with siRNA-ATG7, followed by assessments of autophagy-related genes (LC3Ⅱ/Ⅰ, Beclin-1, ATG7, P62), osteogenic markers (RUNX2, COL1), and osteoclastogenic markers (RANKL, OPG) using WB, RT-qPCR, and autophagy level were detected using immunofluorescence and transmission electron microscopy. Osteogenic differentiation was further evaluated through induction assays. Compressive stress enhanced autophagy in PDLSCs and upregulated both osteogenic and osteoclastogenic markers. However, ATG7 knockdown inhibited autophagy and osteogenic differentiation while promoting the expression of osteoclastogenic markers. These findings demonstrate that ATG7 plays a pivotal role in periodontal remodeling under compressive stress. Its suppression impairs osteogenic differentiation while enhancing osteoclastogenesis, providing insights into the mechanistic interplay between autophagy and mechanotransduction in orthodontic-induced bone remodeling.