Targeting synovial inflammation in knee osteoarthritis: translational insights for diagnosis and therapy

Abstract

Synovial inflammation is a central feature of knee osteoarthritis (OA), linking systemic and local pathogenic pathways with clinical outcomes. This review synthesises current knowledge on synovial structure and function, and the molecular mechanisms that drive synovitis, including metaflammation, mechanoflammation, mechanotransduction, and immune cell polarisation. It further explores how these processes contribute to structural degeneration, pain, and disease progression. Diagnostic approaches are discussed, with emphasis on biochemical biomarkers, imaging modalities, and the limited reliability of pain alone as a disease marker. By integrating clinical phenotypes with molecular endotypes, the review features how precision medicine can reshape OA care. Therapeutic strategies are presented across the translational spectrum, from oral and intra-articular drugs in clinical use to emerging investigational therapies, multitargeting approaches, and novel gene therapies. This review advocates for phenotype- and endotype-informed interventions as a pathway to more effective and personalised management of synovitis-driven knee OA. The translational value of this work lies in integrating molecular mechanisms with clinical strategies to guide early diagnosis, refine therapeutic targeting, and inform the design of future trials.