Skip to main content
Download PDF

Volume 14 Supplement 1

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

Fas deficiency attenuates bone loss during antigen induced arthritis in mice

Arthritis Research & Therapy volume 14, Article number: P38 (2012) Cite this article

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. Methods in Molecular Medicine, Volume 136: Arthritis Research. 2007, Cope AP Totowa (NJ): Humana Press Inc, 2: 243-253.

    Google Scholar 

  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. 10.1073/pnas.0607939103.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  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 Central  CAS  Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Elvira Lazic Mosler, Sania Kuzmac, Sanja Ivcevic, Danka Grcevic & Natasa Kovacic

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

    Sania Kuzmac & Natasa Kovacic

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

    Sanja Ivcevic & Danka Grcevic

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

    Ana Marusic

Authors
  1. Elvira Lazic Mosler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sania Kuzmac
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sanja Ivcevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Danka Grcevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Marusic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Natasa Kovacic
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Mosler, E.L., Kuzmac, S., Ivcevic, S. et al. Fas deficiency attenuates bone loss during antigen induced arthritis in mice. Arthritis Res Ther 14 (Suppl 1), P38 (2012). https://doi.org/10.1186/ar3639

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/ar3639

Keywords

  • Bone Loss
  • Osteoblast Differentiation
  • Trabecular Bone Volume
  • Trabecular Separation
  • Femoral Metaphyses

Arthritis Research & Therapy

ISSN: 1478-6362

Contact us