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

The Journal of Pharmacy and Pharmacology
Ryosuke YoshiokaMasao Murakawa

Abstract

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. 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. 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. CDH11-mediated β-catenin signalling was 42% involved in IL-1β-induced proliferation and had the highest suscept...Continue Reading

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