[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 E_max 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.

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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/