Volume 14 Supplement 1

Proceedings of the 8th Global Arthritis Research Network (GARN) Meeting and 1st Bio-Rheumatology International Congress (BRIC)

Open Access

Fas deficiency attenuates bone loss during antigen induced arthritis in mice

  • Elvira Lazic Mosler1,
  • Sania Kuzmac1, 2,
  • Sanja Ivcevic1, 3,
  • Danka Grcevic1, 3,
  • Ana Marusic4 and
  • Natasa Kovacic1, 2
Arthritis Research & Therapy201214(Suppl 1):P38

DOI: 10.1186/ar3639

Published: 29 February 2012


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.


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.


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.

Authors’ Affiliations

Laboratory for Molecular Immunology, University of Zagreb School of Medicine
Department of Anatomy, University of Zagreb School of Medicine
Department of Physiology and Immunology, University of Zagreb School of Medicine
Department of Research in Biomedicine and Health, University of Split School of Medicine


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

This article is published under license to 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.