Spatial macrophage-fibroblast interactions in osteoarthritis synovium: inflammatory and fibrotic niches

Synovial inflammation and fibrosis often coexist in osteoarthritis, but a transition from one to the other has not been established. This Mini Review examines macrophage-fibroblast interactions in the surface lining, perivascular regions, and collagen-rich synovium. We integrate human spatial and single-cell studies with functional experiments and map reported cell states, markers, locations, and functions. Experimental evidence is clearest for inflammatory amplification. Signals from recruited macrophages can increase fibroblast chemokine and cartilage-degrading enzyme production, while fibroblast secretions and extracellular vesicles influence macrophage recruitment and activation. Oncostatin M can induce inflammatory responses without increasing collagen deposition. Matrix synthesis and mechanical responses characterize fibrotic niches, which may also contain fibroblasts with immunoregulatory functions. These findings favor a model of potentially coexisting niches with overlapping but partly separable inflammatory, matrix-remodeling, and tissue-maintenance functions. Spatial proximity in human tissue identifies candidate signaling partners; it cannot establish their dependence on specific signals or an inflammation-to-fibrosis sequence. We discuss experiments that link defined cellular sources to local responses and measure pain, collagen deposition, clearance of dying cells, and lubrication separately.