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However, the cell interactions and molecular mechanisms of AS enthesitis are still unclear. Herein, we constructed a hind paw loading\/unloading model using experimental spondyloarthritis SKG mice, and generated a single\u2010cell RNA sequencing atlas of mechanical strain\u2010related AS enthesitis. In this context, a disease\u2010specific subpopulation of SDC1\n                    <jats:sup>+<\/jats:sup>\n                    sheath fibroblasts was identified to arise under mechanical strain, and these cells secreted higher levels of CXCL5 to recruit and promote the activation of CXCR4\n                    <jats:sup>hi<\/jats:sup>\n                    neutrophils, which exacerbated CXCR4\n                    <jats:sup>hi<\/jats:sup>\n                    neutrophil\u2010mediated enthesitis by increasing their neutrophil extracellular trap formation. Administering CXCL5 neutralizing antibody relieved disease progression in SKG mice. Additionally, computational trajectory analysis revealed a distinct fate branch of the mechanical strain\u2010responding SDC1\n                    <jats:sup>+<\/jats:sup>\n                    sheath fibroblasts under the control of SOX5\u2010mediated enhancers and super\u2010enhancers. Specifically inhibiting SOX5 in enthesis fibroblasts via rAAV9.HAP\u20101 carrying a shRNA targeting\n                    <jats:italic>Sox5<\/jats:italic>\n                    blocked the generation of SDC1\n                    <jats:sup>+<\/jats:sup>\n                    sheath fibroblasts in response to mechanical strain and markedly reversed the development of CXCR4\n                    <jats:sup>hi<\/jats:sup>\n                    neutrophil\u2010mediated enthesitis. This study identifies the specific cell interactions and molecular mechanisms involved in mechanical strain\u2010related AS enthesitis, therefore contributing to the understanding of AS pathogenesis and providing insight into potential clinical treatments for AS.\n                  <\/jats:p>","DOI":"10.1002\/advs.202520617","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T19:53:36Z","timestamp":1770234816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mechanical Strain\u2010Programmed SDC1\n                    <sup>+<\/sup>\n                    Sheath Fibroblasts Trigger CXCR4\n                    <sup>hi<\/sup>\n                    Neutrophil\u2010Mediated Enthesitis in Ankylosing Spondylitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Jiajie","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Orthopedics The Eighth Affiliated Hospital Sun Yat\u2010sen University  Shenzhen P. 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