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% (P<0.05) and mesenchymal stem cells ∼40% (P<0.05) by 
specifically decreasing the binding of integrins α10β1 and α11β1 to 
arginine-containing motifs, such as GFOGER. In contrast, citrullination had only 
a minor effect on the function of α1β1 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.