To clarify the key role of cellular transdifferentiation in the pathogenesis of chronic gout tophi, and to explore the molecular mechanisms underlying tophus formation, bone destruction and fibrosis, so as to provide theoretical basis and new research directions for targeted therapy of chronic gout and tophus.

By systematic review and analysis, this paper focuses on the microenvironmental characteristics of tophi induced by monosodium urate (MSU) crystal deposition, and summarizes the regulatory effects of related signaling pathways and epigenetic networks.

The formation and progression of tophi rely on local microenvironmental disturbance and cellular phenotypic plasticity caused by MSU crystal deposition. Cellular transdifferentiation, including macrophage polarization, fibroblast-to-myofibroblast transition, abnormal differentiation of mesenchymal stem cells and endothelial-to-mesenchymal transition, is a core cytological event. These processes are modulated by core signaling pathways such as TGF-β/Smad, Wnt/β-catenin, Hedgehog and complex epigenetic regulatory networks.

Cellular transdifferentiation is closely associated with tophus formation, bone destruction and fibrosis in chronic gout. Targeting the related signaling and epigenetic regulatory networks of cellular transdifferentiation is expected to become a novel strategy for the targeted treatment of chronic gout and tophus.