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The previous study of the research group found that monomeric derivatives of paeoniflorin (MDP) can alleviate joint inflammation in adjuvant\u2010induced arthritis (AA) rats by inhibiting macrophage pyroptosis. This study revealed increased levels of hypoxia\u2010inducible factor\u2010 (HIF\u2010) 1\n                    <jats:italic>\u03b1<\/jats:italic>\n                    and N\u2010terminal p30 fragment of GSDMD (GSDMD\u2010N) in fibroblast\u2010like synoviocytes (FLS) of RA patients and AA rats, while MDP significantly inhibited their expression. Subsequently, FLS were exposed to a hypoxic environment or treated with cobalt ion in vitro. Western blot and immunofluorescence analysis showed increased expression of G protein\u2010coupled receptor kinase 2 (GRK2), HIF\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , nucleotide\u2010binding oligomerization segment\u2010like receptor family 3 (NLRP3), ASC, caspase\u20101, cleaved\u2010caspase\u20101, and GSDMD\u2010N. Electron microscopy revealed FLS pyroptosis after exposure in hypoxia. Next, corresponding shRNAs were transferred into FLS to knock down hypoxia\u2010inducible factor\u2010 (HIF\u2010) 1\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , and in turn, NLRP3 and western blot results confirmed the same. The enhanced level of GSDMD was reversed under hypoxia by inhibiting NLRP3 expression. Knockdown and overexpression of GRK2 in FLS revealed GRK2 to be a positive regulator of HIF\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    . Levels of GRK2 and HIF\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    were inhibited by eliminating excess reactive oxygen species (ROS). Furthermore, MDP reduced FLS pyroptosis through targeted inhibition of GRK2 phosphorylation. According to these findings, hypoxia induces FLS pyroptosis through the ROS\/GRK2\/HIF\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \/NLRP3 pathway, while MDP regulates this pathway to reduce FLS pyroptosis.\n                  <\/jats:p>","DOI":"10.1155\/2022\/4566851","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T14:20:09Z","timestamp":1643466009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The ROS\/GRK2\/HIF\u20101\n                    <i>\u03b1<\/i>\n                    \/NLRP3 Pathway Mediates Pyroptosis of Fibroblast\u2010Like Synoviocytes and the Regulation of Monomer Derivatives of 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