State Key Laboratory of Oral Diseases, Department of Pediatric Dentistry, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Stem Cells Dev. 2023 Aug;32(15-16):491-503. doi: 10.1089/scd.2023.0013. Epub 2023 Jun 6.
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 κB (NF-κB) activation, β-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.
保护牙周膜干细胞（PDLSCs）的功能对于牙周炎中的骨再生至关重要。叉头框蛋白 O1（FoxO1）先前已被报道为骨稳态的关键介质，为成骨细胞的增殖和分化提供了有利的环境。在本研究中，我们研究了 FoxO1 激动剂在炎症条件下对 PDLSCs 成骨作用的影响及其机制。在本研究中，我们通过检测 FoxO1 激动剂对 PDLSCs 成骨分化的影响来筛选 FoxO1 激动剂。然后，我们在牙周炎模型中分析了这些激动剂在骨再生中的功能。我们发现，圣草酚或 2-呋喃酰基-LIGRLO-酰胺三氟乙酸盐（2-Fly）通过同时抑制核因子 κB（NF-κB）激活、β-连环蛋白表达和活性氧（ROS）产生，促进炎症下的成骨分化。此外，体内局部注射圣草酚或 2-Fly 可恢复 FoxO1 和 runt 相关转录因子 2（Runx2）的表达，减轻牙槽骨丢失和牙周韧带损伤。这些发现表明，FoxO1 激动剂对 PDLSCs 中的成骨作用具有保护作用，从而促进炎症条件下的骨形成。总之，FoxO1 通过介导多种信号通路可能成为牙周炎骨再生的治疗靶点。
