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

Apoptosis of osteoblasts plays a crucial role in osteomyelitis. Hydrogen sulfide (HS) levels are increased in the pathophysiological processes of osteomyelitis. However, the effect of HS on the apoptosis of osteoblasts remains unclear. To investigate the specific role of HS in osteoblast apoptosis, MC3T3-E1 and hFOB cells were treated with NaHS or NaS, a donor of HS, 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 HS 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. HS increased apoptosis through upregulation of the FAS ligand (FASL) signaling pathway. HS-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 HS on osteogenic differentiation. Hydrogen sulfide promotes LPS-induced apoptosis of osteoblast cells by inhibiting AKT/NF-κB signaling.