Back to Search Start Over

Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a murine model of rheumatoid arthritis

Authors :
Kimito Kawahata
Fumitaka Mizoguchi
Yusuke Matsuo
Nobuyuki Miyasaka
Kouji Matsushima
Satoshi Ueha
Tetsuya Saito
Hitoshi Kohsaka
Yutaka Inagaki
Source :
Biochemical and Biophysical Research Communications. 470:504-509
Publication Year :
2016
Publisher :
Elsevier BV, 2016.

Abstract

Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP and wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G2/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA.

Details

ISSN :
0006291X
Volume :
470
Database :
OpenAIRE
Journal :
Biochemical and Biophysical Research Communications
Accession number :
edsair.doi.dedup.....18744a24215cb6122cfc30f7206978b3
Full Text :
https://doi.org/10.1016/j.bbrc.2016.01.121