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Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines

The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) g...

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Autores principales: Huang, Shan, Thomsson, Kristina A., Jin, Chunsheng, Ryberg, Henrik, Das, Nabangshu, Struglics, André, Rolfson, Ola, Björkman, Lena I., Eisler, Thomas, Schmidt, Tannin A., Jay, Gregory D., Krawetz, Roman, Karlsson, Niclas G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532613/
https://www.ncbi.nlm.nih.gov/pubmed/36213120
http://dx.doi.org/10.3389/fmolb.2022.942406
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author Huang, Shan
Thomsson, Kristina A.
Jin, Chunsheng
Ryberg, Henrik
Das, Nabangshu
Struglics, André
Rolfson, Ola
Björkman, Lena I.
Eisler, Thomas
Schmidt, Tannin A.
Jay, Gregory D.
Krawetz, Roman
Karlsson, Niclas G.
author_facet Huang, Shan
Thomsson, Kristina A.
Jin, Chunsheng
Ryberg, Henrik
Das, Nabangshu
Struglics, André
Rolfson, Ola
Björkman, Lena I.
Eisler, Thomas
Schmidt, Tannin A.
Jay, Gregory D.
Krawetz, Roman
Karlsson, Niclas G.
author_sort Huang, Shan
collection PubMed
description The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. We found consistently 29 markers detected in both plasma and SF. The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation.
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spelling pubmed-95326132022-10-06 Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines Huang, Shan Thomsson, Kristina A. Jin, Chunsheng Ryberg, Henrik Das, Nabangshu Struglics, André Rolfson, Ola Björkman, Lena I. Eisler, Thomas Schmidt, Tannin A. Jay, Gregory D. Krawetz, Roman Karlsson, Niclas G. Front Mol Biosci Molecular Biosciences The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. We found consistently 29 markers detected in both plasma and SF. The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation. Frontiers Media S.A. 2022-09-21 /pmc/articles/PMC9532613/ /pubmed/36213120 http://dx.doi.org/10.3389/fmolb.2022.942406 Text en Copyright © 2022 Huang, Thomsson, Jin, Ryberg, Das, Struglics, Rolfson, Björkman, Eisler, Schmidt, Jay, Krawetz and Karlsson. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Huang, Shan
Thomsson, Kristina A.
Jin, Chunsheng
Ryberg, Henrik
Das, Nabangshu
Struglics, André
Rolfson, Ola
Björkman, Lena I.
Eisler, Thomas
Schmidt, Tannin A.
Jay, Gregory D.
Krawetz, Roman
Karlsson, Niclas G.
Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines
title Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines
title_full Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines
title_fullStr Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines
title_full_unstemmed Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines
title_short Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α: Interplay between O-linked glycosylation and inflammatory cytokines
title_sort truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of vegfa, il-8, and mip-1α: interplay between o-linked glycosylation and inflammatory cytokines
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532613/
https://www.ncbi.nlm.nih.gov/pubmed/36213120
http://dx.doi.org/10.3389/fmolb.2022.942406
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