Hydrogen sulfide promotes lipopolysaccharide-induced apoptosis of osteoblasts by inhibiting the AKT/NF-κB signaling pathway

Abstract

Apoptosis of osteoblasts plays a crucial role in osteomyelitis. Hydrogen sulfide (H₂S) levels are increased in the pathophysiological processes of osteomyelitis. However, the effect of H₂S on the apoptosis of osteoblasts remains unclear. To investigate the specific role of H₂S in osteoblast apoptosis, MC3T3-E1 and hFOB cells were treated with NaHS or Na₂S, a donor of H₂S, and lipopolysaccharide (LPS), during osteomyelitis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry analysis, western blotting, immunofluorescence, polymerase chain reaction, and Alizarin red staining were performed to examine the effects of H₂S on osteoblast cell apoptosis, cell osteogenic differentiation, and AKT kinase (AKT)/nuclear factor kappa B (NF-κB) signaling. Hydrogen sulfide increased cell apoptosis, and inhibited the proliferation and osteogenic differentiation of osteoblast cells impaired by LPS. H₂S increased apoptosis through upregulation of the FAS ligand (FASL) signaling pathway. H₂S-induced apoptosis was alleviated using a FAS/FASL signaling pathway inhibitor. Treatment with NaHS also increased cell apoptosis by downregulating AKT/NF-κB signaling. In addition, treatment with an AKT signaling pathway activator decreased apoptosis and reversed the inhibitory effects of H₂S on osteogenic differentiation. Hydrogen sulfide promotes LPS-induced apoptosis of osteoblast cells by inhibiting AKT/NF-κB signaling.