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

Abstract

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.

• Authors: Ryosuke Yoshioka, Yasuhiro Kita, Asako Nagahira, Atsushi Manno, Naoyuki Makita, Urara Tomita, Masao Murakawa
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 67 Issue 8 Pg. 1075-82 (Aug 2015) ISSN: 2042-7158 [Electronic] England
• PMID: 25787991 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Royal Pharmaceutical Society.

Chemical References

• Cadherins
• Interleukin-1beta
• RNA, Small Interfering
• Tumor Necrosis Factor-alpha
• beta Catenin
• osteoblast cadherin

Topics

• Arthritis, Rheumatoid (physiopathology)
• Cadherins (pharmacology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Enzyme-Linked Immunosorbent Assay
• Female
• Fibroblasts (metabolism)
• Humans
• Interleukin-1beta (pharmacology)
• Male
• RNA, Small Interfering (metabolism)
• Signal Transduction
• Synovial Membrane (physiopathology)
• Tumor Necrosis Factor-alpha (pharmacology)
• beta Catenin (pharmacology)