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Induction of bone loss in DBA/1J mice immunized with citrullinated autologous mouse type II collagen in the absence of adjuvant

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Abstract

Joint damage in rheumatoid arthritis (RA) is characterized by cartilage and bone loss resulting in pain, deformity, and loss of joint function. Anti-citrullinated protein antibody (ACPA) has been implicated in RA pathogenesis and predicts radiographical joint damage and clinical severity. Therefore, the purpose of this study was to assess bone loss by micro-CT, histological joint damage, and ACPA levels using a mouse model of RA. Arthritis was induced by immunizing DBA/1 mice with autologous citrullinated type II mouse collagen (CIT-CII) weekly for 4 weeks. Mice immunized with autologous CII served as controls. At week 5, mice were killed, ACPA levels determined, and micro-CT performed to quantitatively analyze bone damage. Micro-CT analysis revealed significant loss of bone density, volume, and surface (p < 0.05) in bone peripheral to the inflamed joints of CIT-CII animals compared to CII controls. Histological staining demonstrated cartilage, proteoglycan, joint collagen, and bone collagen loss in the CIT-CII group compared to CII. Serum ACPA levels were increased (p = 0.03) in the CIT-CII group compared to CII, and these levels were inversely correlated with bone quantity and quality. In this study, we demonstrate that immunization with autologous CIT-CII initiates significant systemic bone and articular cartilage loss in the absence of adjuvant. Significant inverse correlations of circulating ACPA and bone quality/quantity were present. ACPA levels predict the adverse bone morphological changes in this model of early RA.

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Acknowledgments

We thank the members of the Experimental Immunology Group including: Bartlett C. Hamilton, III, Carlos D. Hunter, and Karen C. Easterling. We also thank the University of Nebraska Medical Center tissue science facility for histological processing of samples. This work was funded by the University of Nebraska Medical Center, Internal Medicine, and Division of Rheumatology.

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Authors and Affiliations

  1. Experimental Immunology Laboratory, Omaha Veterans Administration Medical Center, Omaha, NE, 68105, USA

    Anand Dusad, Michael J. Duryee, Lynell W. Klassen, James R. O’Dell, Ted R. Mikuls & Geoffrey M. Thiele

  2. Experimental Immunology Laboratory, Division of Rheumatology, Department of Internal Medicine, University of Nebraska Medical Center, Wittson Hall Room 3005, Omaha, NE, 68198-6350, USA

    Anand Dusad, Michael J. Duryee, Lynell W. Klassen, James R. O’Dell, Ted R. Mikuls & Geoffrey M. Thiele

  3. Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Dong Wang & Ke Ren

  4. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-6495, USA

    Geoffrey M. Thiele

  5. Experimental Immunology Laboratory, Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, 68198-3025, USA

    Daniel R. Anderson

  6. Department of Medicine, Division of Rheumatology, University of Massachusetts Medical School, Worcester, MA, 01605, USA

    Anita T. Shaw & Ellen M. Gravallese

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  1. Anand Dusad
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Correspondence to Michael J. Duryee.

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Dusad, A., Duryee, M.J., Shaw, A.T. et al. Induction of bone loss in DBA/1J mice immunized with citrullinated autologous mouse type II collagen in the absence of adjuvant. Immunol Res 58, 51–60 (2014). https://doi.org/10.1007/s12026-013-8479-7

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  • DOI: https://doi.org/10.1007/s12026-013-8479-7

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