title: Quantitative analysis of cadherin-11 and β-catenin signalling during proliferation of rheumatoid arthritis-derived synovial fibroblast cells.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., Kobe, Japan.
authors: Ryosuke
authors: R
authors: Yoshioka
authors: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., Kobe, Japan.
authors: Yasuhiro
authors: Y
authors: Kita
authors: Faculty of Drug Discovery Technology, Asubio Pharma Co., Ltd., Kobe, Japan.
authors: Asako
authors: A
authors: Nagahira
authors: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., Kobe, Japan.
authors: Atsushi
authors: A
authors: Manno
authors: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., Kobe, Japan.
authors: Naoyuki
authors: N
authors: Makita
authors: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., Kobe, Japan.
authors: Urara
authors: U
authors: Tomita
authors: Faculty of Exploratory Pharmacology, Asubio Pharma Co., Ltd., Kobe, Japan.
authors: Masao
authors: M
authors: Murakawa
mesh_terms: D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D015820:Cadherins / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D008297:Male; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D013583:Synovial Membrane / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051176:beta Catenin / Q000494:pharmacology*
chemical_list: D015820:Cadherins; D053583:Interleukin-1beta; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; C086960:osteoblast cadherin
keywords: cadherin11; interleukine-1β; rheumatoid arthritis; synovial fibroblast cell; tumour necrosis factor-α