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This article is part of the supplement: Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

Poster presentation

Fas deficiency attenuates bone loss during antigen induced arthritis in mice

Elvira Lazic Mosler1*, Sania Kuzmac12, Sanja Ivcevic13, Danka Grcevic13, Ana Marusic4 and Natasa Kovacic12

  • * Corresponding author: Elvira L Mosler

Author Affiliations

1 Laboratory for Molecular Immunology, University of Zagreb School of Medicine, Zagreb HR-10000, Croatia

2 Department of Anatomy, University of Zagreb School of Medicine, Zagreb HR-10000, Croatia

3 Department of Physiology and Immunology, University of Zagreb School of Medicine, Zagreb HR-10000, Croatia

4 Department of Research in Biomedicine and Health, University of Split School of Medicine, Split HR-21000, Croatia

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Arthritis Research & Therapy 2012, 14(Suppl 1):P38  doi:10.1186/ar3639

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/14/S1/P38


Published:9 February 2012

© 2012 Mosler et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

Antigen induced arthritis (AIA) is an experimental model of rheumatoid arthritis induced by methylated bovine serum albumin (mBSA) [1]. Hyperplastic synovia in AIA contains fibroblast-like synoviocytes (FLS) with reduced ability to differentiate into osteoblasts, chondroblasts or adipocytes [2]. Since Fas is shown to inhibit osteoblast differentiation [3], we were interested whether such inhibitory effect may contribute to the pathogenesis of AIA.

Materials and methods

AIA was induced in mice with a Fas gene knockout (Fas -/-). Three weeks after pre-immunization with mBSA in complete Freund's adjuvant, wild-type (C57BL/6, wt) and Fas -/- mice were injected with mBSA into each knee, whereas controls were injected with equal volume of phosphate buffered saline (PBS). Three weeks after injection we assessed joint diameters, histology, μCT scans, and differentiation of bone marrow- and synovia-derived osteoblasts.

Results

Knee diameters were increased in mBSA-injected wt mice compared to PBS-injected controls (3.21 ± 0.2 vs. 2.98 ± 0.1, p < 0.05, t-test), and this increase was not significant in Fas -/- mice (2.97 ± 0.2 vs. 2.87 ± 0.1). Histology revealed presence of synovial hyperplasia in both mBSA-injected groups, but mBSA-injected wt mice had decreased trabecular bone volume in distal femoral metaphyses (BV/TV) compared to controls (1.08 ± 0.57 vs. 2.55 ± 0.43; p < 0.05, t-test). There was no significant difference between mBSA-injected and control group in Fas -/- mice (2.34 ± 0.62 vs. 2.61 ± 0.65). μCT analysis showed that mBSA-injected wt mice had decreased BV/TV (2.99 ± 0.19 v. 1.96 ± 0.19; p < 0.001, t-test) and trabecular number (TbN) (1.03 ± 0.03 vs. 0.64 ± 0.02), as well as increased trabecular separation (TbSep) (256,89 ± 1395,12 vs. 312.40 ± 1323.91), compared to controls. mBSA injected Fas -/- mice had decreased TbN compared to controls (0.815 ± 0.01 vs. 0.64 ± 0.04; p < 0.05, t-test), with no significant difference in other trabecular parameters. Osteoblast differentiation was increased in both wt and Fas -/- mBSA-injected mice.

Conclusions

Our study demonstrated that Fas deficiency attenuated the development of clinical signs and bone loss in AIA. The mechanisms of this phenomenon need to be clarified.

References

  1. van den Berg WB, et al.: Murine antigen-induced arthritis. In Methods in Molecular Medicine, Volume 136: Arthritis Research. Volume 2. Cope AP Totowa (NJ): Humana Press Inc; 2007::243-253. OpenURL

  2. Li X, Makarov SS: An essential role of NF-kappaB in the "tumor-like" phenotype of arthritic synoviocytes.

    Proc Natl Acad Sci USA 2006, 103:17432-7. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL

  3. Kovacic N, Lukic IK, Grcevic D, Katavic V, Croucher P, Marusic A: The Fas/Fas-ligand system inhibits differentiation of murine osteoblasts but has a limited role in osteoblast and osteoclast apoptosis.

    J Immunol 2007, 178:3379-89. PubMed Abstract | Publisher Full Text | PubMed Central Full Text OpenURL