Refereed journal article or data article (A1)

Joint inflammation related citrullination of functional arginines in extracellular proteins




List of AuthorsSipila KH, Ranga V, Rappu P, Mali M, Pirila L, Heino I, Jokinen J, Kapyla J, Johnson MS, Heino J

PublisherNATURE PUBLISHING GROUP

Publication year2017

JournalScientific Reports

Journal name in sourceSCIENTIFIC REPORTS

Journal acronymSCI REP-UK

Article numberARTN 8246

Volume number7

Number of pages12

ISSN2045-2322

DOIhttp://dx.doi.org/10.1038/s41598-017-08597-4

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/26769324


Abstract
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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Last updated on 2022-07-04 at 16:33