{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:05:42Z","timestamp":1790244342117,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"53","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"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":["82572791 82272521 82302732"],"award-info":[{"award-number":["82572791 82272521 82302732"]}],"id":[{"id":"10.13039\/501100001809","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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Modic changes (MCs) in the lumbar vertebral endplates are a common imaging finding in patients with low back pain. Their pathogenesis and progression are closely linked to the local immune microenvironment, underscoring the need to investigate the immunomodulatory mechanisms involved in MCs. Here, we identified the THBS1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages displaying a strongly pro\u2010inflammatory phenotype. The THBS1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages were enriched at lesion sites in both human lumbar MCs specimens and the C. acnes\u2010induced mouse model of MC. In vitro, C. acnes and its key metabolites promoted THBS1 expression in macrophages via Toll\u2010like receptor (TLR) signaling, while TLR inhibition alleviated MCs by suppressing this macrophage subset. Notably, conditional knockout of THBS1 in macrophages effectively attenuated C. acnes\u2010induced MCs progression. Mechanistically, we identified syndecan\u20104 (SDC4) on endplate chondrocytes as a functional receptor for macrophage\u2010derived THBS1. THBS1\u2013SDC4 engagement activated p38 phosphorylation, leading to transcriptional upregulation of the NLRP3 inflammasome and amplified inflammatory responses in chondrocytes. Conversely, SDC4 silencing mitigated MCs progression. Collectively, this study delineates a mechanism by which THBS1\n                    <jats:sup>+<\/jats:sup>\n                    macrophages exacerbate lumbar endplate MCs through the SDC4\u2013p38\u2013NLRP3 axis. These findings provide a novel theoretical framework and highlight THBS1 and SDC4 as potential immunotherapeutic targets for modulating disc degeneration.\n                  <\/jats:p>","DOI":"10.1002\/advs.76318","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:16:25Z","timestamp":1782476185000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["THBS1\n                    <sup>+<\/sup>\n                    Macrophages Exacerbate Modic Changes via SDC4\u2010Dependent Activation of NLRP3 Inflammasome"],"prefix":"10.1002","volume":"13","author":[{"given":"Xiangxi","family":"Kong","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou P. R. China"},{"name":"Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province  Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qize","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Wound Healing The First Affiliated Hospital of Wenzhou Medical University  Wenzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoan","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Sir Run Run Shaw Hospital Zhejiang University School of Medicine  Hangzhou P. R. China"},{"name":"Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province  Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The Affiliated LiHuiLi Hospital of Ningbo University  Ningbo P. R. 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