痛风是一种常见的关节炎，其特征是尿酸钠 (MSU) 晶体沉积在关节中。滑膜组织中的 MSU 沉积会引发关节炎发作和复发，造成不可逆的关节损伤。然而，MSU晶体在组织中的动态沉积缺乏实验观察。在这项研究中，我们使用化学特异性、无标记的受激拉曼散射 (SRS) 显微镜来研究 MSU 晶体在人类滑膜类器官中的时空沉积和形态特征。我们的研究结果揭示了 MSU 在痛风滑膜内层沉积的关键 12 小时窗口。此外，通过免疫荧光进一步验证了使用 SRS 显微镜观察痛风内膜和亚内滑膜层的独特炎症反应。重要的是，我们发现了亚衬成纤维细胞样滑膜细胞的关键促炎作用，表明需要对这些细胞进行靶向药物治疗。我们的工作有助于对基于密歇根州立大学的疾病的基本理解，并为未来痛风靶向治疗的发展提供宝贵的见解。版权所有 © 2024 Yaxin Chen 等人。

Gout, a common form of arthritis, is characterized by the deposition of monosodium urate (MSU) crystals in joints. MSU deposition in synovial tissues would initiate arthritis flares and recurrence, causing irreversible joint damage. However, the dynamic deposition of MSU crystals in tissues lacks experimental observation. In this study, we used chemical-specific, label-free stimulated Raman scattering (SRS) microscopy to investigate the spatiotemporal deposition and morphological characteristics of MSU crystals in human synovial organoids. Our findings revealed a critical 12-h window for MSU deposition in the lining layer of gouty synovium. Moreover, distinctive inflammatory reactions of the lining and sublining synovial layers in gout using SRS microscopy were further verified by immunofluorescence. Importantly, we identified a crucial proinflammatory role of sublining fibroblast-like synoviocytes, indicating a need for targeted medication treatment on these cells. Our work contributes to the fundamental understanding of MSU-based diseases and offers valuable insights for the future development of targeted gout therapies.Copyright © 2024 Yaxin Chen et al.