{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:48:26Z","timestamp":1791409706192,"version":"4.3.3"},"reference-count":58,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["cstb2022nscq\u2010msx0139"],"award-info":[{"award-number":["cstb2022nscq\u2010msx0139"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The incidence of osteoarthritis (OA) is strongly correlated with aging. It has been shown that the accumulation of senescent cells in the synovium precedes chondrocyte senescence and cartilage degradation, suggesting that synovial cell senescence plays a key role in OA pathogenesis. This study aimed to investigate the mechanisms underlying synovial cell senescence and its influence on intercellular communication within the joint. Using multiplex immunofluorescence, gene regulatory network reconstruction, and single\u2010cell RNA sequencing analyses, we identified senescent cells and characterized the senescence\u2010associated secretory phenotype in the synovium. A series of in vivo and in vitro functional experiments is conducted to elucidate the mechanisms of fibroblast senescence and its effects on macrophages and chondrocytes. We found that synovial intimal fibroblasts (SIF) display more marked premature senescence compared to other synovial cell types. A specific senescent subpopulation within SIF is identified, and we demonstrated that the transcription factors EGR1 and ATF3 regulate senescence\u2010related pathways in these cells. Furthermore, we showed that senescent SIF promote M1 macrophage polarization and cartilage degeneration through paracrine secretion of ANGPTL4. Additionally, senescent SIF may facilitate OA progression through direct cell\u2013cell contact with macrophages.<\/jats:p>","DOI":"10.1002\/advs.202518056","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T05:52:46Z","timestamp":1769147566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Senescent Synovial Intimal Fibroblasts Aggravate Osteoarthritis by Regulating Macrophage Polarization and Chondrocyte Phenotype Through ANGPTL4\u2010\u03b15\u03b21 Axis"],"prefix":"10.1002","volume":"13","author":[{"given":"Muhai","family":"Deng","sequence":"first","affiliation":[{"name":"College of Artificial Intelligence Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiquan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Artificial Intelligence Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Cao","sequence":"additional","affiliation":[{"name":"College of Artificial Intelligence Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Trauma Burns and Combined Injury Department of Wound Infection and Drug Daping Hospital Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengxue","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine The First Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7323-1104","authenticated-orcid":false,"given":"Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Artificial Intelligence Medicine Chongqing Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"issue":"10","key":"e_1_2_10_2_1","first-page":"1500","article-title":"The Incidence and Natural History of Knee Osteoarthritis in the Elderly","volume":"38","author":"Felson D. 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