Physiol Res. 2026 Aug 31;75(4):771-780.
ABSTRACT
Excessive osteoclast activity drives bone-resorptive disorders, and oxidative stress is a key regulator of osteoclast differentiation. Hydrogen sulfide (H?S), an endogenous antioxidant, may modulate this process, but its mechanisms remain unclear. In this study, RANKL (50 ng/mL) was used to induce osteoclastogenesis in RAW264.7 cells, with or without the H?S donor sodium hydrosulfide (NaHS; 50-200 ?M). Osteoclast formation was evaluated by TRAP staining and NFATc1/Cathepsin K expression, while oxidative stress, lipid peroxidation, mitochondrial function, and ferroptosis-related parameters were assessed. Mechanistic studies revealed that NaHS promoted Nrf2 nuclear translocation and upregulated GPX4, HO-1, and NQO1, whereas inhibition of Nrf2 or GPX4 partially reversed these effects. NaHS significantly suppressed osteoclast differentiation, alleviated oxidative stress, and restored mitochondrial function. These findings demonstrate that H?S inhibits RANKL-induced osteoclastogenesis via the Nrf2/GPX4 pathway and suggest this redox axis as a potential therapeutic target for bone-resorptive diseases.
PMID:42708873
