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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2010

Open Access 01-12-2010 | Research article

Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1*/* mice with collagen-induced chronic arthritis

Authors: Caroline Jochems, Ulrika Islander, Malin Erlandsson, Cecilia Engdahl, Marie Lagerquist, Inger Gjertsson, Claes Ohlsson, Rikard Holmdahl, Hans Carlsten

Published in: BMC Musculoskeletal Disorders | Issue 1/2010

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Abstract

Background

Collagen-induced arthritis (CIA) is an often-used murine model for human rheumatoid arthritis (RA). Earlier studies have shown potent anti-arthritic effects with the female sex hormone estradiol and the selective estrogen receptor modulator (SERM) raloxifene in CIA in DBA/1-mice. B10.Q-ncf1*/*mice are B10.Q mice with a mutated Ncf1 gene. In B10.Q-ncf1*/*mice, CIA develops as a chronic relapsing disease, which more accurately mimics human RA. We investigated the role of endogenous and exogenous sex steroids and raloxifene in the course of this model of chronic arthritis. We also examined whether treatment would prevent the development of inflammation-triggered generalized osteoporosis.

Methods

Female B10.Q-ncf1*/*mice were sham-operated or ovariectomized, and CIA was induced. 22 days later, when 30% of the mice had developed arthritis, treatment with raloxifene, estradiol or vehicle was started, and the clinical disease was evaluated continuously. Treatment was continued until day 56 after immunization. At termination of the experiment (day 73), bone mineral density (BMD) was analyzed, paws were collected for histological examination, and sera were analyzed for markers of cartilage turnover and pro-inflammatory cytokines.

Results

Raloxifene and estradiol treatment, as well as endogenous estrogen, decreased the frequency of arthritis, prevented joint destruction and countered generalized osteoporosis. These effects were associated with lower serum levels of the pro-inflammatory cytokine IL-6.

Conclusions

This is the first study to show that raloxifene and estradiol can ameliorate established erosive arthritis and inflammation-triggered osteoporosis in this chronic arthritis model. We propose that treatment with raloxifene could be a beneficial addition to the treatment of postmenopausal RA.
Appendix
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Metadata
Title
Role of endogenous and exogenous female sex hormones in arthritis and osteoporosis development in B10.Q-ncf1*/* mice with collagen-induced chronic arthritis
Authors
Caroline Jochems
Ulrika Islander
Malin Erlandsson
Cecilia Engdahl
Marie Lagerquist
Inger Gjertsson
Claes Ohlsson
Rikard Holmdahl
Hans Carlsten
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2010
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-11-284

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