Osteoarthritis synovium as a nidus for monosodium urate crystal deposition inducing severe gout studied by label-free stimulated Raman scattering combined with synovial organoids

Gout, a common chronic disease, is characterized by the formation and deposition of monosodium urate (MSU) crystal deposition in articular and nonarticular structures. Osteoarthritis (OA), the most prevalent type of arthritis, is a progressive degenerative joint disease. Previous clinical studies have reported that gout frequently affects OA joints; however, the underlying mechanism remains unidentified. Recently, OA synovium has been proposed as a favorable vehicle for MSU crystal deposition. Therefore, this study aimed to investigate whether OA synovium acts as a nidus for MSU crystal deposition inducing severe gout flares, using label-free, highly-specific stimulated Raman scattering (SRS) microscopy combined with innovative preclinical models-synovial organoids. Crystal deposition, cellular phagocytosis, and subsequent inflammation intensity was imaged in ex vivo synovial organoids using SRS microscopy and other biochemical techniques. Results revealed that MSU crystals were more likely to deposit in OA synovium than in normal synovium. Furthermore, OA synoviocytes were more capable of phagocytosing crystals, leading to severe inflammation, and thus, expediting gout. These findings offer a potential explanation for why gout is preferred in OA joints and offer significant insights into the pathophysiology of gout, thereby informing prevention and management strategies for OA to prevent or alleviate the subsequent progression of gout.