Session Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis
Session Type: Abstract Submissions (ACR)
[Background/Purpose ] Cadherin-11 (CDH11) is a cadherin adhesion molecule that anchors b-catenin, and is involved with various functions of synovial fibroblast cells (SFCs) during the development of rheumatoid arthritis (RA). However, the functional mechanism of CDH11 during RA-SFC proliferation is unclear. The aim of our study was to clarify the involvement of CDH11 and b-catenin signaling during human RA-SFC proliferation.
[Methods ] In order to investigate the involvement of CDH11 and b-catenin to proliferation, BrdU incorporation assay with each siRNA treatment was carried out. The effect of knockdown was determined by western blotting and immunohistochemistry. The values of Emax and EC50 in proliferation were caluculated by regression analysis with GraphPad Prism.
[Results ]Using CDH11 specific siRNAs, there were a 42% reduction in IL-1b-induced human RA-SFC proliferation and a 64% reduction in b-catenin protein levels. When b-catenin specific siRNAs were applied, there was a 63% reduction in IL-1b-induced RA-SFC proliferation. The EC50values for IL-1b during RA-SFC proliferation via CDH11-mediated b-catenin-dependent, total b-catenin-dependent, and b-catenin-independent signaling were 0.0015, 0.016, and 0.18 ng/mL, respectively. Blocking homophilic CDH11 ligation with a CDH11 neutralizing antibody did not decrease IL-1b-induced RA-SFC proliferation.
[Conclusion ] CDH11-mediated b-catenin signaling was 42% involved in IL-1b-induced human RA-SFC proliferation and had the highest susceptibility to IL-1b. The mode of action for CDH11 during the cell proliferation was likely associated with a pool of b-catenin protein. In contrast to IL-1b, CDH11 and b-catenin were not involved in TNF-a-induced RA-SFC proliferation.
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/quantitave-analysis-of-cadherin-11-and-beta-catenin-signaling-during-proliferation-of-rheumatoid-arthritis-derived-synovial-fibroblast-cells/