{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T15:17:00Z","timestamp":1788535020699,"version":"build-2803163510"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Osteoarthritis (OA) is one of the most common degenerative joint diseases, and its initiation and progression are closely associated with the inflammatory microenvironment within the joint. As key effector cells of innate immunity in the joint, macrophages contribute to synovial inflammation, cartilage matrix degradation, and impaired tissue repair. Conventional studies have largely interpreted the immunopathology of OA through a binary model of macrophage polarization, in which pro-inflammatory M1 macrophages and anti-inflammatory M2 macrophages are considered opposing functional states. Within this framework, M1\/M2 imbalance is viewed as a major mechanism driving persistent inflammation and cartilage destruction in OA. However, increasing evidence from studies of the ageing-associated immune microenvironment indicates that macrophage states in OA extend well beyond the classical M1\/M2 classification. These states involve the senescence-associated secretory phenotype, functional remodelling of tissue-resident macrophages, metabolism-driven phenotypic transitions, and dynamic regulation through intercellular communication networks. This review summarizes the evidence supporting a conceptual transition from M1\/M2 polarization imbalance to ageing immune microenvironment-driven macrophage state reprogramming in OA. We focus on the underlying molecular mechanisms, cellular interactions, and pathological implications, and further evaluate potential therapeutic strategies based on macrophage functional reprogramming, with the aim of providing a mechanistic and translational basis for precision interventions in OA.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1942715","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T14:31:37Z","timestamp":1788532297000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Paradigm shift in macrophage polarization in osteoarthritis: from M1\/M2 imbalance to macrophage state reprogramming in the ageing immune microenvironment"],"prefix":"10.3389","volume":"17","author":[{"family":"Bandianzhuoma","sequence":"first","affiliation":[{"name":"The University of Queensland","place":["Brisbane, QLD, 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