Abstract | BACKGROUND: 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 indicated that the overexpression of FUT10 contributed to this alteration. Silencing the expression of FUT10 impaired the ability of TNFR1 to bind to TNF-α, impeded activation of the NF-κB and P38/JNK-MAPK pathways, and eventually retarded extracellular matrix (ECM) degradation, senescence, and apoptosis in chondrocytes exposed to TNF-α. CONCLUSION: The elevation of α-1,3 fucosylation is not only a characteristic of OA but also impacts the OA pathological process. Our work provides a new positive feedback loop of " inflammation conditions/TNF-α/FUT10/α-1,3 fucosylation of TNFR1/NF-κB and P38/JNK-MAPK pathways/proinflammatory processes" that contributes to ECM degradation and chondrocyte apoptosis.
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Authors | Hanjie Yu, Mingxiu Li, Xiaodong Wen, Jie Yang, Xiaojun Liang, Xia Li, Xiaojuan Bao, Jian Shu, Xiameng Ren, Wentian Chen, Zheng Li, Yi Li |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 24
Issue 1
Pg. 93
(04 29 2022)
ISSN: 1478-6362 [Electronic] England |
PMID | 35488351
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022. The Author(s). |
Chemical References |
- Lectins
- NF-kappa B
- Receptors, Tumor Necrosis Factor, Type I
- Tumor Necrosis Factor-alpha
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Topics |
- Animals
- Apoptosis
- Cartilage, Articular
(pathology)
- Glycosylation
- Humans
- Inflammation
(pathology)
- Lectins
(metabolism)
- NF-kappa B
(metabolism)
- Osteoarthritis
(metabolism)
- Rabbits
- Receptors, Tumor Necrosis Factor, Type I
(genetics, metabolism)
- Tumor Necrosis Factor-alpha
(metabolism, pharmacology)
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