{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T12:26:27Z","timestamp":1787401587220,"version":"build-2736575974"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202653"],"award-info":[{"award-number":["82202653"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp;amp; Translational Med"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Osteoarthritis (OA) is a widespread degenerative joint disorder marked by irreversible cartilage destruction. While signal transducer and activator of transcription 3 (STAT3) is recognised as a pivotal regulator in its pathogenesis, the downstream regulatory cascades of phosphorylated STAT3 (p\u2010STAT3) in chondrocyte extracellular matrix (ECM) metabolism remain elusive. Our study sought to identify p\u2010STAT3\u2010mediated novel pathways driving OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      P\u2010STAT3 expression was detected in human\/mouse OA cartilage. Chondrocyte\u2010specific STAT3 knockout mice (\n                      <jats:italic>Stat3<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      ;\n                      <jats:italic>Col2a1<\/jats:italic>\n                      <jats:sup>CreERT2<\/jats:sup>\n                      ) were first constructed and used to evaluate OA (spontaneous\/surgically induced). RNA sequencing combined with cleavage under targets and tagmentation sequencing (CUT&amp;Tag\u2010seq) identified p\u2010STAT3 downstream targets, followed by molecular interaction and pathway validation assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>P\u2010STAT3 was significantly upregulated in OA cartilage. STAT3 knockout ameliorated OA progression. Mechanistically, p\u2010STAT3 directly bound the doublecortin\u2010like kinase 1 (DCLK1) promoter to activate its transcription. DCLK1 interacted with IKK\u03b2, promoting IKK\u03b2 phosphorylation and NF\u2010\u03baB activation, ultimately upregulating MMP13 and downregulating COL2A1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies a novel p\u2010STAT3\/DCLK1\/IKK\u03b2\/NF\u2010\u03baB axis that regulates cartilage matrix metabolism and OA progression, suggesting new therapeutic targets for OA intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Doublecortin\u2010like kinase 1 (DCLK1) is identified as a novel phosphorylated signal transducer and activator of transcription 3 (p\u2010STAT3) transcriptional target.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A novel p\u2010STAT3\/DCLK1\/IKK\u03b2\/NF\u2010\u03baB axis regulates chondrocyte extracellular matrix (ECM) metabolism and drives osteoarthritis progression.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Genetic and pharmacological translational evidence validates the p\u2010STAT3\/DCLK1 axis as a prospective therapeutic target against osteoarthritis.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70712","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T06:08:09Z","timestamp":1781590089000},"source":"Crossref","is-referenced-by-count":0,"title":["DCLK1\u2010dependent NF\u2010\u03baB activation mediates p\u2010STAT3\u2010induced osteoarthritis progression"],"prefix":"10.1002","volume":"16","author":[{"given":"Pengfei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chipiu","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery The First Affiliated Hospital of Zhengzhou University  Zhengzhou Henan 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