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CF101 was orally administrated in OA rats induced by anterior cruciate ligament transection (ACLT) surgery, and the rat primary chondrocytes were stimulated by hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, 300\u2009\u03bcM). Histologic grading system was performed for detecting cartilage degeneration and immunohistochemistry for determining pyroptosis. The moleculars associated with cartilage homeostasis and inflammatory cytokines were analysed; moreover, the activation of NLRP3 inflammasome was determined. CF101 treatment significantly attenuated OA cartilage damage, OA\u2010related pain and cartilage pyroptosis. Chondrocytes stimulated by H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> evoked ROS release, thereby promoting the activation of NLRP3 inflammasome and facilitating the cleavage of GSDMD, which ultimately resulted in the mass release of pro\u2010inflammatory cytokines including IL\u20101\u03b2 and IL\u201018, and production of matrix hydrolase. The pre\u2010treatment with CF101 powerfully inhibited the above process both in vivo and in vitro. Our findings demonstrated that activation of A3AR attenuates OA progression and relieves pain perception through suppression of cartilage degradation and inhibition of ROS\/NLRP3\/GSDMD signalling, indicating pyroptosis is a potential candidate for OA treatment.<\/jats:p>","DOI":"10.1111\/jcmm.17438","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T06:46:15Z","timestamp":1656657975000},"page":"4230-4243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Activation of adenosine <scp>A3<\/scp> receptor attenuates progression of osteoarthritis through inhibiting the <scp>NLRP3<\/scp>\/caspase\u20101\/<scp>GSDMD<\/scp> induced signalling"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9013-7873","authenticated-orcid":false,"given":"Hui","family":"Bai","sequence":"first","affiliation":[{"name":"Heilongjiang Key Laboratory for Animal Disease Pathogenesis and Comparative Medicine, College of Veterinary Medicine Northeast Agricultural University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-4350","authenticated-orcid":false,"given":"Zhiheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Heilongjiang Key Laboratory for Animal Disease Pathogenesis and Comparative Medicine, College of Veterinary Medicine Northeast Agricultural University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6196-4845","authenticated-orcid":false,"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Heilongjiang Key Laboratory for Animal Disease Pathogenesis and Comparative Medicine, College of Veterinary Medicine Northeast Agricultural University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2151-9824","authenticated-orcid":false,"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Heilongjiang Key Laboratory for Animal Disease Pathogenesis and Comparative Medicine, College of Veterinary Medicine Northeast Agricultural University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4881-3935","authenticated-orcid":false,"given":"Xiaopeng","family":"Song","sequence":"additional","affiliation":[{"name":"Heilongjiang Key Laboratory for Animal Disease Pathogenesis and Comparative Medicine, College of Veterinary Medicine Northeast Agricultural University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9190-0562","authenticated-orcid":false,"given":"Li","family":"Gao","sequence":"additional","affiliation":[{"name":"Heilongjiang Key Laboratory for Animal Disease Pathogenesis and Comparative Medicine, College of Veterinary Medicine Northeast Agricultural University  Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-00518-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.05.008"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-019-0221-y"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.162"},{"key":"e_1_2_10_6_1","first-page":"1","article-title":"Advances in the molecular mechanisms on Pyroptosis in sepsis","volume":"2018","author":"Wang C","year":"2019","journal-title":"J Pract Shock"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.040"},{"issue":"13","key":"e_1_2_10_8_1","first-page":"R568","article-title":"Walle, Mohamed, Lamkanfi. 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