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  • Huang, ShanGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology (author)

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

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-09-21
  • Frontiers Media SA,2022

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:daf8516c-eef4-4572-b493-8b2959d94938
  • https://lup.lub.lu.se/record/daf8516c-eef4-4572-b493-8b2959d94938URI
  • https://doi.org/10.3389/fmolb.2022.942406DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:151403646URI
  • https://gup.ub.gu.se/publication/322755URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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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  • Thomsson, Kristina A,1969Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xthokr (author)
  • Jin, ChunshengGothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xjinch (author)
  • Ryberg, HenrikSahlgrenska University Hospital (author)
  • Das, NabangshuCumming School of Medicine (author)
  • Struglics, AndréLund University,Lunds universitet,Ortopedi, Lund,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Lund OsteoArthritis Division - Nedbrytning av ledbrosk: en biologisk process som leder till artros,Forskargrupper vid Lunds universitet,Orthopaedics (Lund),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund OsteoArthritis Division - Molecular marker research group,Lund University Research Groups(Swepub:lu)ort-as1 (author)
  • Rolfson, Ola,1973Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för ortopedi,Institute of Clinical Sciences, Department of Orthopaedics(Swepub:gu)xrolol (author)
  • Björkman, Lena I.University of Gothenburg,Sahlgrenska Academy (author)
  • Eisler, ThomasKarolinska Institutet (author)
  • Schmidt, Tannin A.University of Connecticut (author)
  • Jay, Gregory D.Brown University (author)
  • Krawetz, RomanCumming School of Medicine (author)
  • Karlsson, Niclas G.Sahlgrenska Academy,Oslo Metropolitan University (author)
  • Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi (creator_code:org_t)

Related titles

  • In:Frontiers in Molecular Biosciences: Frontiers Media SA92296-889X

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