Pterostilbene Inhibits Ferroptosis And Root Resorption By Targeting Gls2

This study investigates whether ferroptosis occurs in cementoblasts under hypoxia and its role in root resorption, while assessing pterostilbene’s potential to prevent OIIRR (orthodontically induced inflammatory root resorption) by targeting GLS2. A hypoxia model was established in OCCM-30 cells. Ferroptosis markers and morphological changes were assessed via RT-PCR, Western blot, transmission electron microscopy, and immunofluorescence staining. RNA sequencing identified GLS2 as a key regulator, which was further validated through gene silencing and overexpression experiments. Molecular docking was used to screen GLS2-targeting compounds, and the inhibitory effect of pterostilbene on ferroptosis was validated in vitro. Finally, a mouse model of in vivo OIIRR was employed to assess the therapeutic efficacy of pterostilbene. Hypoxia induced ferroptosis in cementoblasts, with GLS2 identified as a key regulator. GLS2 knockdown inhibited ferroptosis by reducing ROS accumulation, iron overload, and restoring cellular antioxidant capacity, whereas its overexpression exacerbated these effects and promoted mitochondrial peroxide accumulation and membrane potential depolarization. Molecular docking and validation experiments confirmed that pterostilbene directly targets GLS2, effectively inhibiting ferroptosis in vitro and significantly alleviating OIIRR in vivo. GLS2 promotes hypoxia-induced ferroptosis in cementoblasts. Pterostilbene inhibits ferroptosis by targeting GLS2, thereby preventing both cementoblast ferroptosis and root resorption.