{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:20:49Z","timestamp":1783128049022,"version":"3.54.6"},"reference-count":0,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cell Physiol Biochem"],"published-print":{"date-parts":[[2018]]},"abstract":"<jats:p>Background\/Aims: Osteoarthritis (OA) is the most common joint disease. Recently, a novel variant near the nuclear receptor coactivator 3 (NCOA3) has been identified in association with greater risk of developing OA. However, how NCOA3 is regulated in chondrocytes and involved in OA pathogenesis remain elusive. Methods: The expression and DNA methylation of NCOA3 in knee OA cartilage and in vitro dedifferentiated chondrocytes with or without rs6094710 SNP were analyzed by qRT-PCR, immunoblotting, methylation-specific PCR and bisulfite sequencing. NCOA3 was depleted by siRNA or shRNA or inhibited by a chemical inhibitor to assess its role in chondrocyte dedifferentiation or OA pathogenesis in posttraumatic OA animal model established by cruciate ligament transection surgery. Results: We found that compared with normal counterparts, samples with rs6094710 SNP failed to upregulate NCOA3. Further evidence associated this phenotype with DNMT1-mediated hypermethylation in gene promoter region. Moreover, we showed that NCOA3 maintained the molecular signature of chondrocytes dedifferentiating in vitro or exposed to IL-1\u03b2, nevertheless, NCOA3 appeared dispensable for preventing OA initiation, since NCOA3 loss did not trigger OA in young mice. Instead, NCOA3 loss promoted posttraumatic OA progression, and in parallel, enhanced NF-\u03baB activation. Finally, the promoted posttraumatic OA progression was significantly retarded when administrated with NF-\u03baB pathway inhibitor, suggesting that NCOA3 lose promotes posttraumatic OA at least partially by enhancing NF-\u03baB activation. Conclusion: Thus, our findings indicate a critical role of NCOA3 in chondrocytes, and imply that manipulating NCOA3 might present a potential therapeutic approach to interfere OA progression.<\/jats:p>","DOI":"10.1159\/000493839","type":"journal-article","created":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T21:02:45Z","timestamp":1538082165000},"page":"2396-2413","source":"Crossref","is-referenced-by-count":13,"title":["NCOA3 Loss Disrupts Molecular Signature of Chondrocytes and Promotes Posttraumatic Osteoarthritis Progression"],"prefix":"10.1159","volume":"49","author":[{"given":"Bing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufeng","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizhao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangbei","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2018,9,27]]},"container-title":["Cellular Physiology and Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/493839","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/493839","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:57:18Z","timestamp":1745427438000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000493839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018]]},"references-count":0,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2018,10,11]]}},"URL":"https:\/\/doi.org\/10.1159\/000493839","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.7140149","asserted-by":"subject"}]},"ISSN":["1015-8987","1421-9778"],"issn-type":[{"value":"1015-8987","type":"print"},{"value":"1421-9778","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018]]}}}