The role of neutrophils in the pathophysiology of knee osteoarthritis

Knee osteoarthritis (KOA) is the most prevalent joint disorder, characterized by progressive damage to cartilage, subchondral bone, and other joint-associated tissues. While mechanical stress remains a core driver, evidence increasingly points to immune-mediated mechanisms as modulators/accelerators of disease progression. Among emerging contributors to KOA progression, neutrophils have recently gained attention for their role in modulating the intra- and periarticular environment. By releasing proteases (e.g. neutrophil elastase, myeloperoxidase), reactive oxygen species, and neutrophil extracellular traps, they create a mechanistic axis that directly cleaves extracellular matrix, induces chondrocyte apoptosis, and sustains fibroblast-like synoviocyte activation. Elevated neutrophil presence in synovial fluid has been associated with a distinct inflammatory KOA endotype, potentially reflecting a more aggressive disease course compared to neutrophil-poor joint environments. Recognizing neutrophils as initiators and amplifiers - rather than bystanders - opens a novel conceptual framework for targeted intervention and precision medicine in osteoarthritis.