Inhibition of NCOA4/FTH1-mediated ferritinophagy attenuates ferroptosis in PDLCs and alleviates orthodontically induced inflammatory root resorption

作者：Liyan Liu, Dongyang Li, Zhe Zhou, Hong Ding, Runze Zhang, Xueyuan Han, Kexin Huang, Chunmiao Jiang · 发表于：Progress in Orthodontics · 年份：2025 · DOI：10.1186/s40510-025-00590-2 · 被引用次数：6 · 研究领域：Ferroptosis and cancer prognosis、Iron Metabolism and Disorders、Bone Metabolism and Diseases

BACKGROUND: Disruption of iron homeostasis is closely associated with ferroptosis and inflammation-related diseases. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy plays a central role in regulating intracellular iron levels and inducing ferroptosis. However, its involvement in orthodontically induced inflammatory root resorption (OIIRR) remains largely unexplored. METHODS : In vitro, a compressive force (CF) loading model was established using human periodontal ligament cells (hPDLCs). Western blotting and immunofluorescence staining were performed to detect the expression of ferroptosis-related proteins, including NCOA4, FTH1, and GPX4. Intracellular levels of malondialdehyde (MDA), Fe²⁺, and reactive oxygen species (ROS) were measured using a ferroptosis assay kit. JC-1 staining was used to evaluate mitochondrial membrane potential. NCOA4 was silenced via lentiviral transfection, and the small-molecule inhibitor 9a was used to further assess its functional role in ferroptosis. In vivo, an OIIRR mouse model was established. Hematoxylin and eosin (H&E) staining, tartrate-resistant acid phosphatase (TRAP) staining, and micro-computed tomography (micro-CT) were used to assess root resorption. The expression of NCOA4, FTH1, and GPX4 in periodontal tissues was evaluated via immunohistochemistry and immunofluorescence. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, was administered intraperitoneally to investigate its therapeutic effect on OIIRR. RESULTS: CF and ...