{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:19:45Z","timestamp":1790741985696,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteoarthritis (OA) is a chronic disorder involving pain and functional disturbance due to its impact on joint tissues. This study investigated the mechanism of the DEAD\u2010box helicase 3 X\u2010linked (DDX3X)\/NOD\u2010like receptor protein 3 (NLRP3)\/gasdermin D (GSDMD) pathway in pyroptosis and inflammatory responses in OA chondrocytes. Mouse chondrocyte ATDC5 cells were cultured in vitro and induced for chondrogenic differentiation, followed by H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    treatment to simulate OA. Cells were transfected for 24\u2009h with siRNA\u2010DDX3X, pcDNA3.1\u2010NLRP3, pcDNA3.1\u2010GSDMD, and corresponding negative controls. Cell viability was evaluated by CCK\u20108. Reactive oxygen species (ROS), interleukin (IL)\u22126, tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), IL\u20101\u03b2, and IL\u201018 levels in the supernatant, DDX3X, GSDMD, and NLRP3 mRNA and protein levels, and pyroptosis\u2010related protein (Collagen II, Aggrecan, Cleave\u2010Caspase\u20101, full\u2010length GSDMD [GSDMD\u2010FL], GSDMD\u2010N\u2010terminal domain [GSDMD\u2010NT], apoptosis\u2010associated spot\u2010like protein [ASC]) levels were assessed by ELISA, RT\u2010qPCR, and western blot. The NLRP3\u2010DDX3X interaction was predicted and validated by the STRING database and Co\u2010IP assay. H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010treated ATDC5 showed decreased cell viability, and Collagen II and Aggrecan levels, increased GSDMD\u2010FL cleavage, supernatant ROS, IL\u20106, TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u201018 levels, DDX3X mRNA and protein expression, Cleave\u2010Caspase\u20101, GSDMD\u2010NT, NLRP3, and ASC levels, and an enhanced NLRP3\u2010DDX3X interaction. However, DDX3X knockdown partially reversed the above phenomenon in H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010treated ATDC5, indicating that suppressing the DDX3X\/GSDMD axis attenuated OA chondrocyte pyroptosis and inflammatory response in vitro. NLRP3 or GSDMD overexpression partly counteracted DDX3X knockdown\u2010improved OA chondrocyte pyroptosis and inflammation. Inhibiting the DDX3X\/NLRP3\/GSDMD axis alleviated chondrocyte pyroptosis and inflammatory response in OA in vitro, thus ameliorating chondrocyte injury.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70618","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T06:20:06Z","timestamp":1766470806000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanism of the DDX3X\/NLRP3\/GSDMD Signaling Axis in Pyroptosis and Inflammatory Response in Osteoarthritis Chondrocytes"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4856-2271","authenticated-orcid":false,"given":"Jun","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongkai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong 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