Disruption of iron homeostasis by HERC2-FTL axis leads to chondrocyte loss and exacerbates osteoarthritis - PubMed
2 hours ago
- #Osteoarthritis
- #Iron homeostasis
- #Ferroptosis
- Disruption of iron homeostasis via the HERC2-FTL axis contributes to chondrocyte loss and worsens osteoarthritis (OA).
- HERC2, an E3 ubiquitin ligase, promotes ferroptosis in OA by degrading ferritin light chain (FTL), leading to iron accumulation and autophagy activation.
- Molecular docking identified proanthocyanidins (PAC) as a potential therapeutic compound targeting HERC2 to mitigate ferroptosis.
- In vitro studies showed that ferroptosis inhibitors (e.g., Liproxstatin-1) and PAC restored redox balance and improved chondrocyte survival under stress.
- HERC2-deficient mice exhibited reduced OA severity, preserved cartilage integrity, and improved joint function after surgery.
- Targeting the HERC2-FTL pathway may offer a disease-modifying approach for OA treatment.