Quantitative analysis of cadherin-11 and β-catenin signalling during proliferation of rheumatoid arthritis-derived synovial fibroblast cells

Objectives Cadherin‐11 (CDH11) is an adhesion molecule that anchors β‐catenin and is involved with various functions of synovial fibroblast cells (SFCs) during the development of rheumatoid arthritis (RA). However, the mechanism of CDH11 during RA‐SFC proliferation is unclear. The aim of our study was to clarify the involvement of CDH11 and β‐catenin signalling during proliferation. Methods IL‐1β‐induced and tumour necrosis factor‐α (TNF‐α)‐induced cell proliferation, with CDH11 siRNAs, β‐catenin‐specific siRNAs and a CDH11‐neutralizing antibody, were assessed by 5‐Bromo‐2'‐deoxy‐uridine ELISA. Key findings Using CDH11 siRNAs, there were a 42% reduction in IL‐1β‐induced proliferation and a 64% reduction in β‐catenin protein. When β‐catenin siRNAs were applied, there was a 63% reduction in IL‐1β‐induced proliferation. The median effective concentration (EC50) values for IL‐1β‐induced proliferation via CDH11‐mediated β‐catenin‐dependent, total β‐catenin‐dependent and β‐catenin‐independent signalling were 0.0015, 0.016 and 0.18 ng/ml, respectively. Blocking CDH11 ligation with a CDH11‐neutralizing antibody did not decrease IL‐1β‐induced proliferation. Conclusions CDH11‐mediated β‐catenin signalling was 42% involved in IL‐1β‐induced proliferation and had the highest susceptibility to IL‐1β among the proliferative signallings analysed in this study. The mode of action for CDH11 during the cell proliferation was likely associated with a pool of β‐catenin protein. In contrast, CDH11 and β‐catenin were not involved in TNF‐α‐induced RA‐SFC proliferation.