Gouty arthritis (GA) is a debilitating autoinflammatory disorder precipitated by the deposition of monosodium urate (MSU) crystals, leading to intense, recurrent joint inflammation and systemic metabolic dysregulation. While hyperuricemia is a prerequisite, the transition to clinical gout involves complex intercellular signaling cascades that are not fully understood. Emerging evidence has identified exosomes,— nanoscale extracellular vesicles, —as critical mediators in this pathological process. Exosomes function as intercellular carriers, transporting a diverse cargo of bioactive molecules, including proteins, lipids, and nucleic acids (e.g., microRNAs), which profoundly influence immune cell activation, inflammasome regulation, and metabolic pathways. This review provides a critical analysis of the dual role of exosomes in both propagating and potentially resolving inflammation in GA. We delve into the intricate mechanisms of exosome-mediated pathogenesis, including the modulation of purine metabolism, lysosomal function, and complement–inflammasome crosstalk. Furthermore, we explore the burgeoning field of exosome-based therapeutics, critically evaluating strategies such as engineered exosomes for targeted drug delivery, mesenchymal stem cell (MSC)-derived exosomes for immunomodulation, and the development of exosomal biomarkers for diagnostics. Additionally, we examine how chemical drugs and herbal compounds may exert therapeutic effects by modulating exosome pathways, offering new insights into integrative treatment approaches. By synthesizing recent findings from proteomic, transcriptomic, and functional studies, we aim to unravel the complexities of exosome signaling in GA and to propose innovative therapeutic avenues that target these pathways to improve patient outcomes.
Zhao et al. (Sun,) studied this question.