{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T12:45:07Z","timestamp":1775997907741,"version":"3.50.1"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteoarthritis (OA) is a prevalent degenerative joint disorder. Paeoniflorin (PF), a primary bioactive compound from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Paeonia lactiflora<\/jats:italic>\n                    <\/jats:styled-content>\n                    roots, demonstrates therapeutic potential for OA. This study investigated the effects and mechanisms of PF in OA. In\u00a0vitro, an OA model was established using interleukin\u20101\u03b2 (IL\u20101\u03b2)\u2010treated chondrocytes. In\u00a0vivo, an OA mouse model was generated via destabilization of the medial meniscus (DMM). Molecular docking, bioinformatics analysis, and experimental validation identified ring finger protein 216 (RNF216) as a PF target. RNF216 overexpression and optineurin (OPTN) overexpression were achieved via genetic manipulation. Autophagy was evaluated by Western blot, transmission electron microscopy, and monomeric red fluorescent protein (mRFP)\u2010green fluorescent protein (GFP)\u2010microtubule\u2010associated protein 1A\/1B\u2010light chain 3 (LC3) reporter. PF attenuated chondrocyte injury in\u00a0vitro and alleviated OA progression in\u00a0vivo. Through molecular docking and cellular thermal shift assay (CETSA), we identified carbonic anhydrase IX (CAIX, CA9) as a direct target of PF. RNF216 overexpression abolished PF's chondroprotective effects, which were rescued by OPTN overexpression. The autophagy inhibitor 3\u2010methyladenine (3\u2010MA) blocked PF\u2010mediated chondroprotection via the RNF216\/OPTN axis. Mechanistically, PF inhibited RNF216\u2010dependent ubiquitination and degradation of OPTN, enhancing autophagic flux to mitigate cartilage damage. PF alleviates OA by suppressing RNF216\u2010mediated OPTN ubiquitination, stabilizing OPTN to activate autophagy and protect chondrocytes. These findings highlight PF as a promising therapeutic agent for OA.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70237","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T18:10:48Z","timestamp":1771265448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paeoniflorin Ameliorates Osteoarthritis via Ring Finger Protein 216\/Optineurin\u2010Mediated Autophagy Activation in Chondrocytes"],"prefix":"10.1111","volume":"107","author":[{"given":"Cheng","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Baoshan Branch Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ding","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shi's Center of Orthopedics and Traumatology Shuguang Hospital Affiliated to Shanghai University 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