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

The inflammatory environment and excessive chondrocyte apoptosis have been demonstrated to play crucial roles in the onset of osteoarthritis (OA). Hydrogen sulfide (H2S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H2S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H2S in the pathogenesis of OA and its protective effects on interleukin (IL)-1 beta-induced chondrocytes were identified. Our data revealed decreased H2S expression in both human degenerative OA cartilage tissue and IL-1 beta-induced chondrocytes. Pretreatment with the H2S donor sodium hydrosulfide (NaHS) dramatically attenuated IL-1 beta-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-kappa B). Moreover, mitochondrial dysfunction-related apoptosis was significantly reversed by NaHS in IL-1 beta-stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL-1 beta-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 H2S may antagonize IL-1 beta-induced inflammation and mitochondrial dysfunction-related apoptosis via selective suppression of the PI3K/Akt/NF-kappa B and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.