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Hydrogen sulfide (H<jats:sub>2<\/jats:sub>S), a gaseous signalling molecule, exerts an inhibitory effect on inflammation and apoptosis in several degenerative diseases. However, the protective effect of H<jats:sub>2<\/jats:sub>S against OA has not been fully clarified, and its underlying mechanism should be examined further. In the current study, the role of endogenous H<jats:sub>2<\/jats:sub>S in the pathogenesis of OA and its protective effects on interleukin (IL)\u20101\u03b2\u2010induced chondrocytes were identified. Our data revealed decreased H<jats:sub>2<\/jats:sub>S expression in both human degenerative OA cartilage tissue and IL\u20101\u03b2\u2010induced chondrocytes. Pretreatment with the H<jats:sub>2<\/jats:sub>S donor sodium hydrosulfide (NaHS) dramatically attenuated IL\u20101\u03b2\u2010induced overproduction of inflammatory cytokines and improved the balance between anabolic and catabolic chondrocyte capacities, and these effects were dependent on PI3K\/AKT pathway\u2010mediated inhibition of nuclear factor kappa B (NF\u2010\u03baB). Moreover, mitochondrial dysfunction\u2010related apoptosis was significantly reversed by NaHS in IL\u20101\u03b2\u2010stimulated chondrocytes. Mechanistically, NaHS partially suppressed IL\u20101\u03b2\u2010induced phosphorylation of the mitogen\u2010activated 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 H<jats:sub>2<\/jats:sub>S may antagonize IL\u20101\u03b2\u2010induced inflammation and mitochondrial dysfunction\u2010related apoptosis via selective suppression of the PI3K\/Akt\/NF\u2010\u03baB and MAPK signalling pathways, respectively, in chondrocytes and may be a potential therapeutic agent for the treatment of OA.<\/jats:p>","DOI":"10.1002\/jcp.30154","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T04:37:26Z","timestamp":1604896646000},"page":"4369-4386","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Hydrogen sulfide protects against IL\u20101\u03b2\u2010induced inflammation and mitochondrial dysfunction\u2010related apoptosis in chondrocytes and ameliorates 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