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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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    Authors
    Dusad, Anand
    Duryee, Michael J.
    Shaw, Anita T.
    Klassen, Lynell W.
    Anderson, Daniel R.
    Wang, Dong
    Ren, Ke
    Gravallese, Ellen M.
    O'Dell, James R.
    Mikuls, Ted R.
    Thiele, Geoffrey M.
    Show allShow less
    UMass Chan Affiliations
    Department of Medicine, Division of Rheumatology
    Document Type
    Journal Article
    Publication Date
    2014-01-01
    Keywords
    Animals
    Arthritis, Rheumatoid
    Bone and Bones
    Collagen Type II
    Hindlimb
    Histocytochemistry
    Image Processing, Computer-Assisted
    Male
    Mice
    Mice, Inbred DBA
    Random Allocation
    X-Ray Microtomography
    Immunopathology
    Musculoskeletal Diseases
    Rheumatology
    Skin and Connective Tissue Diseases
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    Link to Full Text
    http://dx.doi.org/10.1007/s12026-013-8479-7
    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.
    Source
    Immunol Res. 2014 Jan;58(1):51-60. doi: 10.1007/s12026-013-8479-7. Link to article on publisher's site
    DOI
    10.1007/s12026-013-8479-7
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/48750
    PubMed ID
    24371010
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1007/s12026-013-8479-7
    Scopus Count
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