{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:04:45Z","timestamp":1784088285388,"version":"3.55.0"},"reference-count":32,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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 Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a debilitating degenerative joint disease characterized by progressive articular cartilage destruction, persistent inflammation, and functional impairment. Circular RNAs (CireRNAs) have emerged as critical epigenetic regulators in OA pathogenesis; however, the precise functional role of Circ_0003423 in OA remains largely unexplored. This study aimed to elucidate the expression pattern, biological functions, and underlying molecular mechanism of Circ_0003423 in OA progression. Bioinformatic analysis of the GSE178724 dataset was performed to identify differentially expressed CircRNAs in OA cartilage. Circ_0003423 and miR\u2010330\u20105p expression levels were quantified by QRT\u2010PCR in IL\u20101\u03b2\u2013stimulated chondrocytes. The interaction between Circ_0003423 and miR\u2010330\u20105p, and between miR\u2010330\u20105p and TWIST1, was validated by RNA pull\u2010down and dual\u2010luciferase reporter assays. Western blotting was employed to assess TWIST1, Collagen I, Collagen II, ADAMTS5, MMP3, MMP13, total NF\u2010\u03baB p65, and phosphorylated NF\u2010\u03baB p65 (p\u2010NF\u2010\u03baB p65) expression. Chondrocyte proliferation and apoptosis were evaluated by CCK\u20108 and EdU assays and flow cytometry, respectively. Pro\u2010inflammatory cytokine levels were measured by ELISA. An OA mouse model was established via destabilization of the medial meniscus (DMM), and Circ_0003423 was silenced by intra\u2010articular injection of lentiviral shRNA to validate In\u00a0vivo findings. Circ_0003423 was significantly upregulated in OA cartilage and IL\u20101\u03b2\u2013stimulated chondrocytes. Silencing Circ_0003423 rescued IL\u20101\u03b2\u2013induced proliferation inhibition, reduced apoptosis, attenuated pro\u2010inflammatory cytokine secretion, and mitigated ECM degradation. Mechanistically, Circ_0003423 functioned as a ceRNA by directly sponging miR\u2010330\u20105p, which targeted TWIST1 to activate downstream NF\u2010\u03baB signalling and upregulate ADAMTS5, MMP3, and MMP13, with concomitant collagen downregulation. Rescue experiments confirmed that miR\u2010330\u20105p inhibition or TWIST1 overexpression abrogated the protective effects of circ_0003423 silencing. In\u00a0vivo, circ_0003423 silencing upregulated miR\u2010330\u20105p, suppressed TWIST1\/NF\u2010\u03baB\/MMP3\/MMP13 activation, and alleviated cartilage degeneration, chondrocyte apoptosis, and inflammatory responses in DMM mice. Circ_0003423 drives OA progression by functioning as a ceRNA to sponge miR\u2010330\u20105p, thereby de\u2010repressing TWIST1 and activating downstream NF\u2010\u03baB signalling and MMP3\/MMP13\u2010mediated ECM destruction. Targeting circ_0003423 represents a promising therapeutic strategy for OA intervention.<\/jats:p>","DOI":"10.1111\/jcmm.71278","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T04:13:45Z","timestamp":1783397625000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circular\n                    <scp>RNA<\/scp>\n                    circ_0003423 Promotes Osteoarthritis Progression by Sponging\n                    <scp>miR<\/scp>\n                    \u2010330\u20105p to Upregulate\n                    <scp>TWIST1<\/scp>\n                    \u2010Mediated Chondrocyte Inflammation and Extracellular Matrix Degradation"],"prefix":"10.1111","volume":"30","author":[{"given":"Lei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Putuo Hospital, Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Putuo People's Hospital, School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Putuo Hospital, Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Putuo Hospital, Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics Putuo Hospital, Shanghai University of Traditional Chinese Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2761-4478","authenticated-orcid":false,"given":"Fei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics Putuo People's Hospital, School of Medicine, Tongji University  Shanghai 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