The role of altered glycosylation in human nucleus pulposus cells in inflammation and degeneration

Joyce, Kieran; Isa, Isma Liza Mohd; Krouwels, Anita; Creemers, Laura B.; Devitt, Aiden; Pandit, Abhay

doi:10.22203/ecm.v041a26

Cited by 17 publications

(18 citation statements)

References 62 publications

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“…Altered fucosylation has been observed in a number of in ammatory conditions, and inhibition of fucosylation could modulate human nucleus pulposus cell protein translation of catabolic enzymes in response to in ammation [39,40]. Our ndings revealed that α-1,3/6 fucosylation is characteristic of OA chondrocytes.…”

Section: Discussionmentioning

confidence: 57%

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

Wen

et al. 2022

Preprint

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Background: Osteoarthritis (OA) is characterized by ECM degradation in chondrocytes and inflammation of the synovial membrane. Fucosylation is a main type of glycosylation, and is involved in a variety of pathological processes, including inflammation and cancer. However, whether fucosylation impacts the OA process is unknown. Methods: Total proteins were extracted from cartilage samples obtained from patients with OA (n = 11), OA rabbit models at different time points (n = 12). The OA-associated abnormal glycopatterns were evaluated by lectin microarray and lectin blot. Expression of fucosyltransferases involved in the synthesis of α-1,3 fucosylation were assessed by semi-qPCR. The α-1,3 fucosylation mediated by FUT10 was interrupted by transfection of siRNA; and the effect of α-1,3 fucosylation on OA-associated events was assessed. The TNFR1 antibody microarray was fabricated to investigate the effect of α-1,3 fucosylation on the binding ability of TNFR1 to TNF-α.Results: Elevated α-1,3 fucosylation is observed in cartilage from OA patients, rabbit models and chondrocytes induced by TNF-α (fold change> 2, p< 0.01). The overexpression of FUT10 contributes to this alteration. Downregulation of FUT10 impaired the binding ability of TNFR1 to TNF-α, impeded activation of the NF-κB and P38/JNK-MAPK pathways and eventually retarded ECM degradation, senescence and apoptosis of chondrocytes induced by TNF-α. Conclusion: The elevation of α-1,3 fucosylation is not only a characteristic of OA but also impacts the OA 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 apoptosis of chondrocytes.

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Section: Discussionmentioning

confidence: 57%

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

Wen

et al. 2022

Preprint

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“…Notwithstanding the relatively low number of publications relating to glycosylation of the IVD, a recent study of the changes in the glycosylation in degenerative NP reported hyper sialylation and core fucosylation in a cytokine‐mediated inflammation model 57 . However, the effect of aging may have been obscured by comparing degenerative mature NP with healthy young NP, with the assumption that the glycosylation patterns of interest in mature discs are universal.…”

Section: Discussionmentioning

confidence: 99%

An insight on the N‐glycome of notochordal cell‐rich porcine nucleus pulposus during maturation

et al. 2023

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Degeneration of the intervertebral disc is an age‐related condition. It also accompanies the disappearance of the notochordal cells, which are remnants of the developmental stages of the nucleus pulposus (NP). Molecular changes such as extracellular matrix catabolism, cellular phenotype, and glycosaminoglycan loss in the NP have been extensively studied. However, as one of the most significant co‐ and posttranslational modifications, glycosylation has been overlooked in cells in degeneration. Here, we aim to characterize the N‐glycome of young and mature NP and identify patterns related to aging. Accordingly, we isolated N‐glycans from notochordal cell‐rich NP from porcine discs, characterized them using a combined approach of exoglycosidase digestions and analysis with hydrophilic interaction ultra‐performance liquid chromatography and mass spectrometry. We have assigned over 300 individual N‐glycans for each age group. Moreover, we observed a notable abundance of antennary structures, galactosylation, fucosylation, and sialylation in both age groups. In addition, as indicated from our results, increasing outer arm fucosylation and decreasing α(2,3)‐linked sialylation with aging suggest that these traits are age‐dependent. Lastly, we have focused on an extensive characterization of the N‐glycome of the notochordal cell‐rich NP in aging without inferred degeneration, describing glycosylation changes specific for aging only. Our findings in combination with those of other studies, suggest that the degeneration of the NP does not involve identical processes as aging.

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“…Concerning glycosylation, the altered N-glycome, may play a role in inflammation and disease progression (Joyce et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Alterations of bovine nucleus pulposus cells with aging

et al. 2023

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Aging is one of the major etiological factors driving intervertebral disc (IVD) degeneration, the main cause of low back pain. The nucleus pulposus (NP) includes a heterogeneous cell population, which is still poorly characterized. Here, we aimed to uncover main alterations in NP cells with aging. For that, bovine coccygeal discs from young (12 months) and old (10–16 years old) animals were dissected and primary NP cells were isolated. Gene expression and proteomics of fresh NP cells were performed. NP cells were labelled with propidium iodide and analysed by flow cytometry for the expression of CD29, CD44, CD45, CD146, GD2, Tie2, CD34 and Stro‐1. Morphological cell features were also dissected by imaging flow cytometry. Elder NP cells (up‐regulated bIL‐6 and bMMP1 gene expression) presented lower percentages of CD29+, CD44+, CD45+ and Tie2+ cells compared with young NP cells (upregulated bIL‐8, bCOL2A1 and bACAN gene expression), while GD2, CD146, Stro‐1 and CD34 expression were maintained with age. NP cellulome showed an upregulation of proteins related to endoplasmic reticulum (ER) and melanosome independently of age, whereas proteins upregulated in elder NP cells were also associated with glycosylation and disulfide bonds. Flow cytometry analysis of NP cells disclosed the existence of 4 subpopulations with distinct auto‐fluorescence and size with different dynamics along aging. Regarding cell morphology, aging increases NP cell area, diameter and vesicles. These results contribute to a better understanding of NP cells aging and highlighting potential anti‐aging targets that can help to mitigate age‐related disc disease.

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The role of altered glycosylation in human nucleus pulposus cells in inflammation and degeneration

Cited by 17 publications

References 62 publications

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

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

An insight on the N‐glycome of notochordal cell‐rich porcine nucleus pulposus during maturation

Alterations of bovine nucleus pulposus cells with aging

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