Chen Ziyi, Wang Wenjuan, Chen Yaxin, Ji Minbiao, Hu Yinghui
Department of Sports Medicine Huashan Hospital Fudan University Shanghai China.
State Key Laboratory of Surface Physics and Department of Physics Human Phenome Institute Multiscale Research Institute of Complex Systems Academy for Engineering and Technology Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education) Fudan University Shanghai China.
MedComm (2020). 2025 Jan 5;6(1):e70040. doi: 10.1002/mco2.70040. eCollection 2025 Jan.
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.
痛风是一种常见的慢性疾病，其特征是单钠尿酸盐（MSU）晶体在关节和非关节结构中形成并沉积。骨关节炎（OA）是最常见的关节炎类型，是一种进行性退行性关节疾病。以往的临床研究报告称，痛风常累及骨关节炎关节；然而，其潜在机制仍不明晰。最近，有人提出骨关节炎滑膜是MSU晶体沉积的有利载体。因此，本研究旨在利用无标记、高特异性的受激拉曼散射（SRS）显微镜结合创新的临床前模型——滑膜类器官，研究骨关节炎滑膜是否作为MSU晶体沉积的病灶，引发严重的痛风发作。使用SRS显微镜和其他生化技术，对离体滑膜类器官中的晶体沉积、细胞吞噬作用以及随后的炎症强度进行成像。结果显示，MSU晶体在骨关节炎滑膜中比在正常滑膜中更易沉积。此外，骨关节炎滑膜细胞更有能力吞噬晶体从而导致严重炎症，进而加速痛风。这些发现为痛风在骨关节炎关节中更易发生提供了一个潜在的解释，并为痛风的病理生理学提供了重要见解，从而为骨关节炎的预防和管理策略提供依据，以预防或减轻痛风随后的进展。
