Ferroptosis
Ferroptosis is a form of programmed cell death driven by iron and the oxidation of fats in cell membranes (lipid peroxidation). It is held back by glutathione and the glutathione-dependent enzyme GPX4.
Also called iron-dependent cell death.
Ferroptosis is an iron-dependent cell death associated with the peroxidation of lipids (Miao 2022). Cells stop it largely through GPX4, which needs glutathione to work, so a cell short of glutathione is more exposed.
Gene-activity, chemical and microscope analyses linked ferroptosis closely to osteoarthritis, and two ferroptosis blockers, ferrostatin-1 and the iron-binding drug deferoxamine, protected against it in lab and animal models (Miao 2022). Osteoarthritic cartilage from patients had less GPX4 than undamaged cartilage (Miao 2022).
In cartilage cells under mechanical stress, NAC delivered in targeted nanoparticles restored glutathione and suppressed ferroptosis, and it protected mouse knees (Wang 2026). Dihydrolipoic acid suppressed ferroptosis in mouse cartilage cells exposed to an inflammatory signal (Chen 2026).
Sources
- Miao Y, Chen Y, Xue F et al. Contribution of ferroptosis and GPX4's dual functions to osteoarthritis progression. EBioMedicine 2022.
- Wang S, Zhang F, Zhou X et al. Chondrocyte-Targeted Nanoparticles Loaded with N-Acetylcysteine Protect Articular Cartilage and Attenuate Osteoarthritis by Inhibiting Ferroptosis via Glutathione Maintenance. Small Sci 2026.
- Chen Y, Fang J, Zhou Z et al. Dihydrolipoic acid suppresses ferroptosis in chondrocytes to ameliorate the progression of osteoarthritis by modulating the FOXO1/TXNIP signaling pathway. Free Radic Biol Med 2026.
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