Background: Orthodontic tooth movement can be caused by the remodeling of periodontal tissues, which is initiated by mechanical forces. Understanding the response of periodontal ligament stem cells (PDLSCs) is crucial for enhancing orthodontic treatment methods. Autophagy serves as an intrinsic defense mechanism that protects cells from mechanical stress caused by environmental changes. This study aims to explore the autophagic mechanism of PDLSCs under orthodontic compression force.

Methods: In this study, static compression force was applied to stimulate PDLSCs. Cell viability and apoptosis were assessed through Cell Counting Kit-8 assay and flow cytometry. Alkaline phosphatase staining and Alizarin red staining assays were used to examine osteogenic differentiation. Autophagy and osteogenic differentiation-related proteins were measured by means of Western blotting.

Results: Progranulin (PGRN) was expressed at high levels in PDLSCs exposed to compression force (p < 0.001). Autophagy and osteogenic differentiation of PDLSCs could be induced by compression force (p < 0.01). Moreover, the autophagy and osteogenic differentiation of compression force-stimulated PDLSCs was further enhanced upon PGRN overexpression (p < 0.01), while silencing of PGRN contributed to diametrically opposite results (p < 0.05). Mechanistically, high levels of PGRN exerted an inhibitory impact on the expression of phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway-related proteins (p < 0.01). Furthermore, treatment with insulin-like growth factor-1 (IGF-1), a specific agonist, reversed the facilitating impacts of PGRN overexpression on autophagy and osteogenic differentiation (p < 0.05).

Conclusions: Our findings shed light on a novel autophagic mechanism of PDLSCs under orthodontic compression force and demonstrate that the inhibitory role of PGRN on the PI3K/AKT/mTOR pathway, thereby mediating the autophagy and osteogenic differentiation of compression force-stimulated PDLSCs. This may offer a new insight for periodontal remodeling during orthodontic treatment.