Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis
Abstract 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 proces...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-022-02776-z |
| _version_ | 1818263964101902336 |
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| author | Hanjie Yu Mingxiu Li Xiaodong Wen Jie Yang Xiaojun Liang Xia Li Xiaojuan Bao Jian Shu Xiameng Ren Wentian Chen Zheng Li Yi Li |
| author_facet | Hanjie Yu Mingxiu Li Xiaodong Wen Jie Yang Xiaojun Liang Xia Li Xiaojuan Bao Jian Shu Xiameng Ren Wentian Chen Zheng Li Yi Li |
| author_sort | Hanjie Yu |
| collection | DOAJ |
| description | Abstract 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 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. |
| first_indexed | 2024-12-12T19:27:22Z |
| format | Article |
| id | doaj.art-672201ad63264b7e9b011a9a683e823c |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-12T19:27:22Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-672201ad63264b7e9b011a9a683e823c2022-12-22T00:14:29ZengBMCArthritis Research & Therapy1478-63622022-04-0124111410.1186/s13075-022-02776-zElevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosisHanjie Yu0Mingxiu Li1Xiaodong Wen2Jie Yang3Xiaojun Liang4Xia Li5Xiaojuan Bao6Jian Shu7Xiameng Ren8Wentian Chen9Zheng Li10Yi Li11Laboratory for Functional Glycomics, College of Life Sciences, Northwest UniversityThe Second Clinical Medical College of Shaanxi University of Chinese MedicineDepartment of Foot and Ankle Surgery, Honghui Hospital, Xi’an Jiaotong UniversityDepartment of Foot and Ankle Surgery, Honghui Hospital, Xi’an Jiaotong UniversityDepartment of Foot and Ankle Surgery, Honghui Hospital, Xi’an Jiaotong UniversityLaboratory for Functional Glycomics, College of Life Sciences, Northwest UniversityLaboratory for Functional Glycomics, College of Life Sciences, Northwest UniversityLaboratory for Functional Glycomics, College of Life Sciences, Northwest UniversityLaboratory for Functional Glycomics, College of Life Sciences, Northwest UniversityLaboratory for Functional Glycomics, College of Life Sciences, Northwest UniversityLaboratory for Functional Glycomics, College of Life Sciences, Northwest UniversityDepartment of Foot and Ankle Surgery, Honghui Hospital, Xi’an Jiaotong UniversityAbstract 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 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.https://doi.org/10.1186/s13075-022-02776-zOsteoarthritisChondrocyteα-1,3 FucosylationFUT10TNF-αTNFR1 |
| spellingShingle | Hanjie Yu Mingxiu Li Xiaodong Wen Jie Yang Xiaojun Liang Xia Li Xiaojuan Bao Jian Shu Xiameng Ren Wentian Chen Zheng Li Yi Li Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis Arthritis Research & Therapy Osteoarthritis Chondrocyte α-1,3 Fucosylation FUT10 TNF-α TNFR1 |
| title | Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis |
| title_full | Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis |
| title_fullStr | Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis |
| title_full_unstemmed | Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis |
| title_short | Elevation of α-1,3 fucosylation promotes the binding ability of TNFR1 to TNF-α and contributes to osteoarthritic cartilage destruction and apoptosis |
| title_sort | elevation of α 1 3 fucosylation promotes the binding ability of tnfr1 to tnf α and contributes to osteoarthritic cartilage destruction and apoptosis |
| topic | Osteoarthritis Chondrocyte α-1,3 Fucosylation FUT10 TNF-α TNFR1 |
| url | https://doi.org/10.1186/s13075-022-02776-z |
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