Hydrogen sulfide protects against IL-1β-induced inflammation and mitochondrial dysfunction-related apoptosis in...

The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H₂ S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H₂ S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H₂ S in the pathogenesis of OA and its protective effects on interleukin (IL)-1β-induced chondrocytes were identified. Our data revealed decreased H₂ S expression in both human degenerative OA cartilage tissue and IL-1β-induced chondrocytes. Pretreatment with the H₂ S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1β-induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K/AKT pathway-mediated inhibition of nuclear factor kappa B (NF-κB). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1β-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) cascades. Furthermore, in the destabilization of the medial meniscus mouse model, OA progression was ameliorated by NaHS administration. Taken together, these results suggest that H₂ S may antagonize IL-1β-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-κB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.