title: Evaluation of cartilage and bone degradation in a murine collagen antibody-induced arthritis model.
abstract: The purpose of this work was to validate collagen antibody-induced arthritis (CAIA) model in two mice strains (Balb/c and CD-1) using clinical, biochemical, microstructural and histological techniques. We induced arthritis in mice using a cocktail of collagen type II (CII) antibodies followed by an injection with lipopolysaccharide (LPS) in different doses in Balb/c and CD-1 mice strains. Serum CTX-II levels were measured at study termination and correlated with microscopic severity of joint lesions as determined by a validated scoring systems. Bone involvement was assessed by microcomputer tomography (micro-CT). Balb/c mice developed rapid (day 6) and robust (100%) arthritis, whereas CD-1 mice showed only temporary macroscopic signs of disease. Serum CTX-II levels in Balb/c mice showed a significant increase in cartilage degradation in diseased animals (43-64% compared with non-diseased mice) and was decreased in animals receiving dexamethasone. Correlation of serum CTX-II with the microscopic score was statistically significant (P < 0.01). Micro-CT analysis demonstrated structural damage in bone in the CAIA Balb/c mice, which was prevented by dexamethasone. The CAIA-LPS model provides a useful supplement to currently available animal models of arthritis. This is a rapid onset and robust model; however, the choice of mouse strain should be evaluated carefully.
authors.affiliation: Nordic Bioscience A/S, Herlev Hovedgade 207, Herlev, DK-2730, Denmark. soe@nordicbioscience.com
authors.forename: S
authors.initials: S
authors.lastname: Oestergaard
authors.forename: K E
authors.initials: KE
authors.lastname: Rasmussen
authors.forename: N
authors.initials: N
authors.lastname: Doyle
authors.forename: A
authors.initials: A
authors.lastname: Varela
authors.forename: L
authors.initials: L
authors.lastname: Chouinard
authors.forename: S Y
authors.initials: SY
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Qvist
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D001842:Bone and Bones / Q000473:pathology; D002356:Cartilage / Q000473:pathology; D024043:Collagen Type II / Q000276:immunology*; D003907:Dexamethasone / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice / Q000235:genetics / Q000276:immunology*; D008807:Mice, Inbred BALB C; D014057:Tomography, X-Ray Computed
chemical_list: D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D024043:Collagen Type II; D008070:Lipopolysaccharides; D003907:Dexamethasone