Citrullination of collagen II affects integrin-mediated cell adhesion in a receptor-specific manner

Sipil?K.; HaagS.; DenessioukK.Kap?yl?J.PetersE.C.DenesyukA.HansenU.KonttinenY.JohnsonM.S.HolmdahlR.HeinoJ.

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Citrullination of collagen II affects integrin-mediated cell adhesion in a receptor-specific manner

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Citrullinated collagen II (CII) is a well-known autoantigen in rheumatoid arthritis (RA). However, the direct effects of CII citrullination on cell behavior have not been described. To study whether citrullination of CII could affect cellular functions, we measured the adhesion of 3 different cell types (human Saos2 osteosarcoma cells, human synovial fibroblasts, and rat mesenchymal stem cells) with impedance-based technology. The binding of different collagen receptor integrins to citrullinated collagen was studied by CHO cell lines, each overexpressing 1 of the 4 human collagen receptors on the cell surface, and with solid-phase binding assays, using the recombinant human integrin α1I, α2I, α10I, and α11I domains. Collagen citrullination decreased the adhesion of synovial fibroblasts ～50 (P0.05) and mesenchymal stem cells ～40 (P0.05) by specifically decreasing the binding of integrins α10β1 and α11β 1 to arginine-containing motifs, such as GFOGER. In contrast, citrullination had only a minor effect on the function of α 1β1 and α2β1 integrins, which have been reported to play a critical role in regulating leukocyte function. Molecular modeling was used to explain the detected functional differences at the structural level. Given that the integrins regulate cell metabolism, proliferation, and migration, we suggest that collagen citrullination modifies the pathogenesis of RA. Here, CII citrullination was shown to decrease the survival of mesenchymal stem cells.

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《The FASEB Journal》 |2014年第8期|3758-3768|共11页
作者
Sipil?K.; HaagS.; DenessioukK.Kap?yl?J.PetersE.C.DenesyukA.HansenU.KonttinenY.JohnsonM.S.HolmdahlR.HeinoJ.;
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作者单位

Department of Biochemistry, University of Turku, Turku, Finland;

Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics;

Structural Bioinformatics Laboratory, Biochemistry, Department of Bioscience, ?bo AkademiGenomics Institute, Novartis Research Foundation, San Diego, CA, United StatesDepartment of Physiology, Chemistry, and Pathobiochemistry, Muenster University Hospital, MuensterDepartment of Medicine, Institute of Clinical Medicine, University of Helsinki, Helsinki, FinlandMedicity Research Laboratory, University of Turku, Turku, Finland, Division of Medical Inflammation;

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正文语种英语
中图分类生物化学;
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PAD; Rheumatoid arthritis;

Citrullination of collagen II affects integrin-mediated cell adhesion in a receptor-specific manner

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