Ferroptosis Inhibition Enhances Osteoblast Activity: The Role of Liproxstatin-1 and Coenzyme Q10

Ferroptosis, a form of regulated cell death triggered by lipid peroxidation, is implicated in various degenerative diseases and bone regeneration. In this study, we hypothesized that the ferroptosis inhibitors Liproxstatin-1 (Lip-1) and Coenzyme Q10 (CoQ10) play a dual role in protecting cells against ferroptotic damage and promoting osteogenic differentiation in MC3T3-E1 cells. Erastin-induced ferroptosis significantly reduced cell viability and increased lipid peroxidation, as evidenced by BODIPY™ 581/591 C11 staining. Both Lip-1 and CoQ10 decreased lipid peroxidation and restored cell viability, particularly at early treatment points. Post-treatment recovery experiments showed that both agents reversed erastin-induced damage, with Lip-1 having a stronger and more sustained effect. ALP activity assays on day 14 revealed dose-dependent increases with Lip-1 and moderate stimulation with CoQ10, indicating additional osteoinductive properties. Moreover, cell density affected sensitivity to lipid peroxidation, with higher cell densities providing protection through antioxidant pooling. These results highlight CoQ10 and Lip-1 as promising candidates for bone tissue engineering, as they offer protection against ferroptosis and promote osteoblast differentiation. Overall, this study emphasizes the therapeutic potential of ferroptosis modulators for bone regeneration.