{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:09:01Z","timestamp":1788761341069,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100012547","name":"Natural Science Foundation of Guangxi Zhuang Autonomous Region","doi-asserted-by":"publisher","award":["2025GXNSFHA069017"],"award-info":[{"award-number":["2025GXNSFHA069017"]}],"id":[{"id":"10.13039\/100012547","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020084","name":"Guangzhou Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["2024A04J9995"],"award-info":[{"award-number":["2024A04J9995"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515140035"],"award-info":[{"award-number":["2023A1515140035"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Fibroblast\u2010like synoviocytes (FLS) in rheumatoid arthritis (RA) synovium acquire a unique aggressive phenotype and produce cytokines that perpetuate inflammation and proteases that contribute to cartilage destruction. Actin\u2010bundling protein Fascin\u20101 (FSCN1) is involved in FLS migration and invasion, but its role and mechanism in FLS phenotypic activation remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>FSCN1 expression was analyzed in the synovium from healthy controls (n = 6), patients with RA (n = 6), and patients with osteoarthritis (n = 6) with written informed consent obtained before sample collection, as well as synovium from control (n = 6) and arthritic mice (n = 6). Transcriptome profiling, RNA immunoprecipitation sequencing, and mass spectrometry analysis were performed to determine the underlying mechanism. FLS\u2010specific FSCN1 knockout, FSCN1 intra\u2010articular overexpression mice, and FSCN1 inhibitors were used to characterize the role and therapeutic potential of FSCN1 in experimental arthritis (n = 5\u20138).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FSCN1 was significantly increased in RA synovium and predominantly localized to PDPN\u2010positive FLS (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). FSCN1 overexpression enhanced F\u2010actin remodeling, FLS migration, invasion, proliferation, and inflammatory activation and exacerbated synovitis and cartilage damage in arthritis mouse models (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0026). Conversely, FLS\u2010specific FSCN1 ablation reduced knee swelling, pain\u2010related behavior, synovial inflammation, and Osteoarthritis Research Society International scores in arthritis mouse models (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.0196). Mechanistically, FSCN1 promoted F\u2010actin fiber formation, spatially sequestered tripartite motif\u2013containing protein 38 (TRIM38), inhibited TRIM38\u2010mediated IGF2BP1 ubiquitination, and sustained PI3K\u2010AKT\/NF\u2010\u03baB signaling. The FSCN1 inhibitors imipramine and NP\u2010G2\u2010044 suppressed FLS activation and alleviated arthritis pathology in mice (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pharmacologic inhibition of FSCN1 restrains synovial inflammation and joint destruction by suppressing the aggressive phenotype change of FLS, representing a promising therapeutic strategy against RA.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70300-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70300","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:27:43Z","timestamp":1787030863000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>FSCN1<\/scp>\n                    Promotes Rheumatoid Arthritis Progression via Inhibiting TRIM38\u2013Mediated Ubiquitination of\n                    <scp>IGF2BP1<\/scp>\n                    in Fibroblast\u2010Like Synoviocytes"],"prefix":"10.1002","author":[{"given":"Liangyu","family":"Chen","sequence":"first","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital Southern Medical University  Guangzhou Guangdong China"},{"name":"Orthopedics and Sports Medicine Center, Beijing Tsinghua Changgung Hospital School of Clinical Medicine, Tsinghua University  P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Wu","sequence":"additional","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilin","family":"Zou","sequence":"additional","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinwei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalin","family":"Chen","sequence":"additional","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghao","family":"Li","sequence":"additional","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Yang","sequence":"additional","affiliation":[{"name":"Academy of Orthopedics, Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third School of Clinical Medicine, Southern Medical University, The Third Affiliated Hospital Southern Medical University  Guangzhou Guangdong 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