Targeting YAP1‐regulated Glycolysis in Fibroblast‐Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression

Abstract: 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.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Targeting YAP1‐regulated Glycolysis in Fibroblast‐Like Synoviocytes Impairs Macrophage Infiltration to Ameliorate Diabetic Osteoarthritis Progression ; day:03 ; month:12 ; year:2023 ; extent:20 ; Advanced science ; (03.12.2023) (gesamt 20)

Contributors, Places and Time

• Creator: 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

Further information

• DOI: 10.1002/advs.202304617
• URN: urn:nbn:de:101:1-2023120414395559858206
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:37 AM CEST