| Autor: |
Yang, Jie, Li, Shanshan, Li, Zhenyan, Yao, Lutian, Liu, Meijing, Tong, Kui‐Leung, Xu, Qiutong, Yu, Bo, Peng, Rui, Gui, Tao, Tang, Wang, Xu, Yidi, Chen, Jiaxu, He, Jun, Zhao, Kewei, Wang, Xiaogang, Wang, Xiaoying, Zha, Zhengang, Zhang, Huan‐Tian |
| Předmět: |
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| Zdroj: |
Advanced Science; 2/2/2024, Vol. 11 Issue 5, p1-20, 20p |
| Abstrakt: |
The interplay between immune cells/macrophages and fibroblast‐like synoviocytes (FLSs) plays a pivotal role in initiating synovitis; however, their involvement in metabolic disorders, including diabetic osteoarthritis (DOA), is largely unknown. In this study, single‐cell RNA sequencing (scRNA‐seq) is employed to investigate the synovial cell composition of DOA. A significant enrichment of activated macrophages within eight distinct synovial cell clusters is found in DOA synovium. Moreover, it is demonstrated that increased glycolysis in FLSs is a key driver for DOA patients' synovial macrophage infiltration and polarization. In addition, the yes‐associated protein 1 (YAP1)/thioredoxin‐interacting protein (TXNIP) signaling axis is demonstrated to play a crucial role in regulating glucose transporter 1 (GLUT1)‐dependent glycolysis in FLSs, thereby controlling the expression of a series of adhesion molecules such as intercellular adhesion molecule‐1 (ICAM‐1) which may subsequently fine‐tune the infiltration of M1‐polarized synovial macrophages in DOA patients and db/db diabetic OA mice. For treatment, M1 macrophage membrane‐camouflaged Verteporfin (Vt)‐loaded PLGA nanoparticles (MVPs) are developed to ameliorate DOA progression by regulating the YAP1/TXNIP signaling axis, thus suppressing the synovial glycolysis and the infiltration of M1‐polarized macrophages. The results provide several novel insights into the pathogenesis of DOA and offer a promising treatment approach for DOA. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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