{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:17:26Z","timestamp":1788175046570,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,6,14]],"date-time":"2016-06-14T00:00:00Z","timestamp":1465862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology, Japan","doi-asserted-by":"crossref","award":["23689004"],"award-info":[{"award-number":["23689004"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Activating transcription factor 3 (Atf3) has been implicated in the pathogenesis of various diseases, including cancer and inflammation, as well as in the regulation of cell proliferation and differentiation. However, the involvement of Atf3 in developmental skeletogenesis and joint disease has not been well studied to date. Here, we show that Atf3 is a critical mediator of osteoarthritis (OA) development through its expression in chondrocytes. <jats:italic>ATF3<\/jats:italic> expression was markedly up\u2010regulated in the OA cartilage of both mice and humans. Conditional deletion of Atf3 in chondrocytes did not result in skeletal abnormalities or affect the chondrogenesis, but alleviated the development of OA generated by surgically inducing knee joint instability in mice. Inflammatory cytokines significantly up\u2010regulated Atf3 expression through the nuclear factor\u2010kB (NF\u2010kB) pathway, while cytokine\u2010induced interleukin\u20106 (<jats:italic>Il6<\/jats:italic>) expression was repressed, in ATF3\u2010deleted murine and human chondrocytes. Mechanistically, Atf3 deficiency decreased cytokine\u2010induced <jats:italic>Il6<\/jats:italic> transcription in chondrocytes through repressing NF\u2010kB signalling by the attenuation of the phosphorylation status of IkB and p65. These findings suggest that Atf3 is implicated in the pathogenesis of OA through modulation of inflammatory cytokine expression in chondrocytes, and the feed\u2010forward loop of inflammatory cytokines\/NF\u2010kB\/Atf3 in chondrocytes may be a novel therapeutic target for the treatment for OA. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4739","type":"journal-article","created":{"date-parts":[[2016,5,9]],"date-time":"2016-05-09T13:56:56Z","timestamp":1462802216000},"page":"426-437","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["ATF3 deficiency in chondrocytes alleviates osteoarthritis development"],"prefix":"10.1002","volume":"239","author":[{"given":"Takashi","family":"Iezaki","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences Kanazawa University Graduate School of Medical, Pharmaceutical and Health Sciences  Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kakeru","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Pharmacology, Division of Pharmaceutical Sciences Kanazawa University Graduate School of Medical, Pharmaceutical and 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