{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T14:58:31Z","timestamp":1792249111873,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Bone destruction associated with active rheumatoid arthritis (RA) remains a major therapeutic challenge, with a lack of reliable molecular markers reflecting bone injury. This study aims to identify novel biomarkers linked to bone destruction in active RA through proteomic analysis, providing new strategies for precise monitoring and targeted therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Data\u2010independent acquisition mass spectrometry was used for proteomic quantification and bioinformatic analysis on plasma samples from 160 patients with RA and 40 healthy controls. Key proteins associated with bone destruction were screened by integrating Sharp scores with synovial single\u2010cell RNA sequencing data and subsequently validated in two independent cohorts (N\n                      <jats:sub>1<\/jats:sub>\n                      = 50 and N\n                      <jats:sub>2<\/jats:sub>\n                      = 10) using enzyme\u2010linked immunosorbent assay and multiplex immunohistochemistry. Functional studies were conducted using fibroblast\u2010like synoviocytes (FLSs) in vitro and a collagen\u2010induced arthritis (CIA) mouse model in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 4,998 plasma proteins were identified, with 506 showing significant differential expression between active and remitted RA. Thousand\u2010and\u2010one\u2013amino acid kinase 3 (TAOK3) levels were positively associated with Sharp scores and markedly elevated in patients with active RA. Combining TAOK3 with C\u2010reactive protein improved diagnostic accuracy for active RA (area under the curve = 0.915). High TAOK3 expression was also associated with increased relapse frequency. Functional studies showed that TAOK3 knockdown suppressed the tumor\u2010like phenotype of FLSs and down\u2010regulated matrix metalloproteinase 1\/2\/3 and cathepsin K, whereas TAOK3 overexpression promoted pannus cell\u2013mediated bone erosion, mitigated by TAOK3\u2010targeted inhibitor. In vivo, its inhibition showed therapeutic effects in CIA mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TAOK3 serves as a potential biomarker for bone destruction in active RA and as a therapeutic target for precision monitoring and intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70020","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T02:39:22Z","timestamp":1766457562000},"page":"1045-1061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Plasma Proteomics Identifies Thousand\u2010and\u2010One\u2013Amino Acid Kinase 3 as a Potential Biomarker of Rheumatoid Arthritis Activity and a Novel Therapeutic Target"],"prefix":"10.1002","volume":"78","author":[{"given":"Pengfei","family":"Xin","sequence":"first","affiliation":[{"name":"Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai China"},{"name":"The Research Institute for Joint Diseases, Shanghai Academy of Traditional Chinese Medicine  Shanghai China"},{"name":"Longhua Hospital Shanghai University of Traditional Chinese Medicine, Jiangxi Hospital  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhen","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai\u2010MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"A","sequence":"additional","affiliation":[{"name":"Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine  Shanghai 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