Hydrogen sulfide is a novel regulator implicated in glucocorticoids-inhibited bone formation

Glucocorticoids contribute to the increased incidence of secondary osteoporosis. Hydrogen sulfide (H(2)S) is a gasotransmitter and plays an essential role in bone metabolism. In this study, we investigated the therapeutic effects of H(2)S on glucocorticoid-induced osteoporosis (GIO). We found that dexamethasone (Dex) decreased serum H(2)S and two key H(2)S-generating enzymes in the bone marrow in vivo, cystathione b-synthase and cystathione g-lyase. Treatment of H(2)S-donor GYY4137 in rat significantly relieved the inhibitory effect of Dex on bone formation. Dex inhibited osteoblasts proliferation and osteogenic differentiation and decreased the expressions of the two H(2)S-generating enzymes. Further investigation showed that H(2)S was involved in Dex-mediated osteoblasts proliferation, differentiation, and apoptosis. Mechanistically, GYY4137 promoted osteoblastogenesis by activating Wnt signaling through increased production of the Wnt ligands. In comparison, the blockage of Wnt/β-catenin signaling pathway significantly alleviated the effect of H(2)S on osteoblasts. In conclusion, the restoration of H(2)S levels is a potential novel therapeutic approach for GIO.