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In the early stage of immune activation, pre-antigenic regulatory signals act before classical antigen presentation and influence how DCs shape joint immunity. Increased extracellular matrix (ECM) stiffness activates the Integrin-FAK-NF-\u03baB pathway, driving inflammatory or exhausted DC states. ECM fragments and damage-associated molecular patterns (DAMPs) stimulate pattern recognition receptors (PRRs), inducing cytokines that sustain chronic inflammation. Hypoxia, lactate, and oxidative stress reprogram DC metabolism, suppress IL-12, and promote Th17 responses. Targeting these upstream factors offers new therapeutic opportunities. Strategies that modify matrix stiffness, block DAMP-mediated signaling, or restore metabolic balance can help reset DC function and preserve joint homeostasis. Emerging biomaterial-based approaches further provide a foundation for immune-restorative and regenerative therapies. In the future, integrating DC-modulatory materials with personalized immune profiling may enable precise immuno-regenerative treatments for OA, representing a shift from symptom relief to immune-guided cartilage repair.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1749150","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:22:42Z","timestamp":1770355362000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pre-antigenic regulatory signals in osteoarthritis: modulators of dendritic cell activation and joint immune balance"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiabao","family":"Liang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew 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