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Targeting YAP1‐regulated Glycolysis in Fibroblast‐Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression
AbstractThe 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.
Targeting YAP1‐regulated Glycolysis in Fibroblast‐Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression
AbstractThe 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.
Targeting YAP1‐regulated Glycolysis in Fibroblast‐Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression
Advanced Science
Yang, Jie (author) / Li, Shanshan (author) / Li, Zhenyan (author) / Yao, Lutian (author) / Liu, Meijing (author) / Tong, Kui‐Leung (author) / Xu, Qiutong (author) / Yu, Bo (author) / Peng, Rui (author) / Gui, Tao (author)
Advanced Science ; 11
2024-02-01
Article (Journal)
Electronic Resource
English