Induction of bone loss in DBA/1J mice immunized with citrullinated autologous mouse type II collagen in the absence of adjuvant
Department of Medicine, Division of Rheumatology
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
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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Citation: Immunol Res. 2014 Jan;58(1):51-60. doi: 10.1007/s12026-013-8479-7. Link to article on publisher's site
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.; and Thiele, Geoffrey M., "Induction of bone loss in DBA/1J mice immunized with citrullinated autologous mouse type II collagen in the absence of adjuvant" (2014). Rheumatology Publications and Presentations. 48.