Mengjia Wang, Changyun Sun, Hongrui Liu, Xin Zhang, Jiahao Zhang, Qiaohui Ying, Yongwei Wu, Zichen Zhao, Fanke Wang, Jie Guo
Our findings suggest that the RUNX1/GPX4 signalling axis may be a potential therapeutic target during orthodontic tooth movement that can promote alveolar bone remodelling by inhibiting ferroptosis in OTM.
BACKGROUND: The adaptive remodelling of alveolar bone ensures the effectiveness and stability of orthodontic tooth movement (OTM), but how to accurately regulate the remodelling of alveolar bone is the focus of orthodontic research. Ferroptosis plays an important role in bone remodelling.
METHODS: Immunohistochemical analysis was employed to assess the expression of ferroptosis-related proteins GPX4 and ACSL4 to investigate ferroptosis induction on the compressive side during orthodontic treatment. Subsequently, proteomic analysis was conducted on GPX4 knockdown MC3T3-E1 cells to identify potential transcription factors. Dual luciferase and ChIP-qPCR assays were utilised to examine the GPX4 promoter region. Furthermore, the impact of RUNX1 modulation was evaluated through both in vitro and in vivo experiments.
RESULTS: The application of compressive force led to a significant decrease in GPX4 expression in alveolar bone, suggesting that ferroptosis contributes to osteoblast death under compressive force. Analysis using the JASPAR database revealed that RUNX1, a transcription factor associated with RUNt, may play a crucial role in regulating glutathione peroxidase 4 (GPX4), a key marker of ferroptosis during orthodontic tooth movement (OTM). ChIP-qPCR results confirmed the binding of RUNX1 to the GPX4 promoter region, and treatment with the RUNX1 agonist kartogenin effectively rescued the osteogenic loss induced by GPX4 reduction. Modulation of GPX4 levels did not reverse the decrease in RUNX1 expression. Additionally, examination of osteogenic changes in MC3T3-E1 cells under compressive force following kartogenin treatment demonstrated that increased levels of RUNX1 contributed to increasing osteogenic levels under compressive force conditions.
CONCLUSION: Our findings suggest that the RUNX1/GPX4 signalling axis may be a potential therapeutic target during orthodontic tooth movement that can promote alveolar bone remodelling by inhibiting ferroptosis in OTM.