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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 4/2014

Open Access 01-08-2014 | Research article

The role of total and cartilage-specific estrogen receptor alpha expression for the ameliorating effect of estrogen treatment on arthritis

Authors: Cecilia Engdahl, Anna E Börjesson, Huamei F Forsman, Annica Andersson, Alexandra Stubelius, Andree Krust, Pierre Chambon, Ulrika Islander, Claes Ohlsson, Hans Carlsten, Marie K Lagerquist

Published in: Arthritis Research & Therapy | Issue 4/2014

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Abstract

Introduction

Estrogen (E2) delays onset and decreases severity of experimental arthritis. The aim of this study was to investigate the importance of total estrogen receptor alpha (ERα) expression and cartilage-specific ERα expression in genetically modified mice for the ameliorating effect of estrogen treatment in experimental arthritis.

Methods

Mice with total (total ERα-/-) or cartilage-specific (Col2α1-ERα-/-) inactivation of ERα and wild-type (WT) littermates were ovariectomized, treated with E2 or placebo, and induced with antigen-induced arthritis (AIA). At termination, knees were collected for histology, synovial and splenic cells were investigated by using flow cytometry, and splenic cells were subjected to a T-cell proliferation assay.

Results

E2 decreased synovitis and joint destruction in WT mice. Amelioration of arthritis was associated with decreased frequencies of inflammatory cells in synovial tissue and decreased splenic T-cell proliferation. E2 did not affect synovitis or joint destruction in total ERα-/- mice. In Col2α1-ERα-/- mice, E2 protected against joint destruction to a similar extent as in WT mice. In contrast, E2 did not significantly ameliorate synovitis in Col2α1-ERα-/- mice.

Conclusions

Treatment with E2 ameliorates both synovitis and joint destruction in ovariectomized mice with AIA via ERα. This decreased severity in arthritis is associated with decreased synovial inflammatory cell frequencies and reduced splenic T-cell proliferation. ERα expression in cartilage is not required for estrogenic amelioration of joint destruction. However, our data indicate that ERα expression in cartilage is involved in estrogenic effects on synovitis, suggesting different mechanisms for the amelioration of joint destruction and synovitis by E2.
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Metadata
Title
The role of total and cartilage-specific estrogen receptor alpha expression for the ameliorating effect of estrogen treatment on arthritis
Authors
Cecilia Engdahl
Anna E Börjesson
Huamei F Forsman
Annica Andersson
Alexandra Stubelius
Andree Krust
Pierre Chambon
Ulrika Islander
Claes Ohlsson
Hans Carlsten
Marie K Lagerquist
Publication date
01-08-2014
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 4/2014
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar4612

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