Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis

作者：Hanjie Yu, Mingxiu Li, Xiaodong Wen, Jie Yang, Xiaojun Liang, Xia Li, Xiaojuan Bao, Jian Shu, Xiameng Ren, Wentian Chen, Zheng Li, Yi Li · 发表于：Arthritis Research & Therapy · 年份：2022 · DOI：10.1186/s13075-022-02776-z · 被引用次数：26 · 研究领域：Osteoarthritis Treatment and Mechanisms、Glycosylation and Glycoproteins Research、Studies on Chitinases and Chitosanases

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis and is characterized by the degradation of articular cartilage and inflammation of the synovial membrane. Fucosylation is an important feature of protein N/O-glycosylation and is involved in a variety of pathological processes, including inflammation and cancer. However, whether fucosylation impacts the OA pathological process is unknown. METHODS: Total proteins were extracted from cartilage samples obtained from patients with OA (n = 11) and OA rabbit models at different time points (n = 12). OA-associated abnormal glycopatterns were evaluated by lectin microarrays and lectin blots. The expression of fucosyltransferases involved in the synthesis of α-1,3 fucosylation was assessed by semi-qPCR. The synthesis of α-1,3 fucosylation mediated by FUT10 was interrupted by the transfection of siRNA, and the effect of α-1,3 fucosylation on OA-associated events was assessed. Then, immunoprecipitation and lectin blotting were used to investigate the relationship between the α-1,3 fucosylation level of tumor necrosis factor receptor superfamily member 1A (TNFR1) and OA. Finally, a TNFR1 antibody microarray was fabricated to evaluate the effect of α-1,3 fucosylation on the ability of TNFR1 to bind to tumor necrosis factor-α (TNF-α). RESULTS: Elevated α-1,3 fucosylation was observed in cartilage from OA patients, rabbit models, and chondrocytes induced by TNF-α (fold change> 2, p< 0.01). Our results and the GEO database ...