Forkhead Box Protein O1 Agonists Promote Bone Regeneration in Periodontitis by Protecting the Osteogenesis of Periodontal Ligament Stem Cells

Protecting the function of periodontal ligament stem cells (PDLSCs) is crucial for bone regeneration in periodontitis. Forkhead box protein O1 (FoxO1) has been previously reported as a crucial mediator in bone homeostasis, providing a favorable environment for osteoblast proliferation and differentiation. In this study, we investigated the effect and mechanism of FoxO1 agonists on the osteogenesis of PDLSCs under inflammatory conditions. In this study, we screened FoxO1 agonists by detecting their effects on the osteogenic differentiation of PDLSCs. Then, the function of these agonists in bone regeneration was analyzed in the periodontitis model. We found that hyperoside or 2-furoyl-LIGRLO-amide trifluoroacetate salt (2-Fly) promoted osteogenic differentiation under inflammation by simultaneously inhibiting nuclear factor kappa B (NF-kappa B) activation, beta-catenin expression, and reactive oxygen species (ROS) production. Moreover, local injection of hyperoside or 2-Fly rescued the expression of FoxO1 and runt-related transcription factor 2 (Runx2) in vivo, alleviating alveolar bone loss and periodontal ligament damage. These findings suggested that FoxO1 agonists exerted a protective effect on osteogenesis in PDLSCs, as a result, facilitating bone formation under inflammatory conditions. Taken together, FoxO1 might serve as a therapeutic target for bone regeneration in periodontitis by mediating multiple signaling pathways.

Automated summary

The activation of Forkhead box protein O1 (FoxO1) promotes osteogenesis of periodontal ligament stem cells (PDLSCs) and protects their function under inflammatory conditions. Hyperoside or 2-furoyl-LIGRLO-amide trifluoroacetate salt (2-Fly) enhances osteogenic differentiation by inhibiting NF-kappa B activation, beta-catenin expression, and ROS production. Local injection of hyperoside or 2-Fly rescues the expression of FoxO1 and Runx2 in vivo, alleviating alveolar bone loss and periodontal ligament damage. These findings demonstrate the protective effect of FoxO1 agonists on osteogenesis in PDLSCs and their potential for bone regeneration in periodontitis.