A1 Refereed original research article in a scientific journal
Joint inflammation related citrullination of functional arginines in extracellular proteins
Authors: Sipila KH, Ranga V, Rappu P, Mali M, Pirila L, Heino I, Jokinen J, Kapyla J, Johnson MS, Heino J
Publisher: NATURE PUBLISHING GROUP
Publication year: 2017
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: ARTN 8246
Volume: 7
Number of pages: 12
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-017-08597-4(external)
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/26769324(external)
We report the extent, specific sites and structural requirements of joint inflammation related citrullination in extracellular proteins. A total of 40 synovial fluid samples derived from chronically inflamed human joints were analysed by heparin-agarose fractionation and LC-MS/MS. Citrullination of 55 arginines in extracellular proteins was detected. Importantly, 20% of the sites have a characterized function related to the hallmarks of destructive joint inflammation. E.g. four arginine residues, shown here to be citrullinated, are also affected by mutations in inherited diseases causing haemolysis or blood clotting dysfunction. Citrullination of integrin ligands was selected for further studies since fibronectin R234 in isoDGR was among the most frequently citrullinated arginines in synovial fluid. Assays with synovial fibroblasts and integrin alpha V beta 3 indicated decreased affinity to the enzymatically citrullinated integrin binding sites. To conclude, our data indicate that in inflamed joints extensive citrullination affects the functional arginine residues in extracellular proteins.
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