Neutrophils in spondyloarthritis pathogenesis: from inflammatory infiltration to bone remodeling

Spondyloarthritis (SpA) is a group of autoimmune diseases characterized by chronic inflammation and pathological new bone formation in the axial skeleton, yet the mechanisms linking inflammatory microenvironment to aberrant osteogenesis remain incompletely understood. Emerging evidence indicates that neutrophils, traditionally viewed as acute inflammatory effectors, play a pivotal role throughout the disease course. Specifically, activated neutrophils can secrete BMPs and may respond to Wnt signaling and they may indirectly promote osteogenic differentiation of mesenchymal stem cells, while NET formation may create a pro-osteogenic niche. The synergistic action of these signals may induce aberrant osteogenic differentiation of mesenchymal stem cells, ultimately contributing to pathological osteophyte formation and spinal ankylosis. This review synthesizes current evidence to propose a testable working model of neutrophil involvement from inflammation initiation to ectopic ossification in SpA, evaluates the therapeutic potential and challenges of targeting neutrophils, and outlines directions for future translational research.