Induction of bone loss in DBA/1J mice immunized with citrullinated autologous mouse type II collagen in the absence of adjuvant
Authors
Dusad, AnandDuryee, 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.
UMass Chan Affiliations
Department of Medicine, Division of RheumatologyDocument Type
Journal ArticlePublication Date
2014-01-01Keywords
AnimalsArthritis, 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
Metadata
Show full item recordAbstract
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 siteDOI
10.1007/s12026-013-8479-7Permanent Link to this Item
http://hdl.handle.net/20.500.14038/48750PubMed ID
24371010Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1007/s12026-013-8479-7