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Truncated lubricin ...
Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α : Interplay between O-linked glycosylation and inflammatory cytokines
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- Huang, Shan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Thomsson, Kristina A, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Jin, Chunsheng (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
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- Ryberg, Henrik (author)
- Sahlgrenska University Hospital
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- Das, Nabangshu (author)
- Cumming School of Medicine
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- Struglics, André (author)
- Lund 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
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- Rolfson, Ola, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för ortopedi,Institute of Clinical Sciences, Department of Orthopaedics
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- Björkman, Lena I. (author)
- University of Gothenburg,Sahlgrenska Academy
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- Eisler, Thomas (author)
- Karolinska Institutet
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- Schmidt, Tannin A. (author)
- University of Connecticut
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- Jay, Gregory D. (author)
- Brown University
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- Krawetz, Roman (author)
- Cumming School of Medicine
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- Karlsson, Niclas G. (author)
- Sahlgrenska Academy,Oslo Metropolitan University
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(creator_code:org_t)
- 2022-09-21
- 2022
- English.
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In: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 9
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- cytokines
- glycobiology
- glycoprotein
- lubricin/proteoglycan 4
- mucin-domains
- mucins
- osteoarthritis
- Tn antigen
Publication and Content Type
- art (subject category)
- ref (subject category)
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To the university's database
- By the author/editor
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Huang, Shan
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Thomsson, Kristi ...
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Jin, Chunsheng
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Ryberg, Henrik
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Das, Nabangshu
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Struglics, André
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show more...
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Rolfson, Ola, 19 ...
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Björkman, Lena I ...
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Eisler, Thomas
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Schmidt, Tannin ...
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Jay, Gregory D.
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Krawetz, Roman
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Karlsson, Niclas ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Rheumatology and ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
- Articles in the publication
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Frontiers in Mol ...
- By the university
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Lund University
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Karolinska Institutet
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University of Gothenburg