Clinical and histopathological characterization of a large animal (ovine) model of collagen-induced arthritis.
Collagen induced arthritis (CIA) is the most studied and used rheumatoid arthritis (RA) model in animals, as it shares many pathological and immunological features of the human disease. The aim of this study was to characterize clinical and immunological aspects of the ovine CIA model, and develop lameness and histopathological scoring systems, in order to validate this model for use in therapeutic trials. Sheep were sensitized to bovine type II collagen (BCII), arthritis was induced by injection of bovine collagen type II into the hock joint and the response was followed for two weeks. Clinical signs of lameness and swelling were evident in all sheep and gross thickening of the synovium surrounding the tibiotarsal joint and erosion on the cartilage surface in the arthritic joints. Leucocyte cell counts were increased in synovial fluid and there was synovial hyperplasia, thickening of the intimal layer, inflammation and marked angiogenesis in the synovial tissue. There was a large influx of monocytes and lymphocytes into the synovial tissue, and increased expression of TNF-α and IL-1β in arthritic intima, angiogenesis and upregulation of VCAM-1. CIA in sheep appears to be an excellent large animal model of RA and has the potential for testing biological therapeutics for the treatment of rheumatoid arthritis.
Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
A
A
Abdalmula
Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
E A
EA
Washington
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia.
J V
JV
House
Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
L M
LM
Dooley
Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.
B A
BA
Blacklaws
Mesoblast Ltd., Victoria, Australia.
P
P
Ghosh
Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia. Electronic address: bais@unimelb.edu.au.
S R
SR
Bailey
Faculty of Veterinary Science, University of Melbourne, Parkville, Victoria, Australia.
W G
WG
Kimpton
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D024043:Collagen Type II; D005260:Female; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000276:immunology; D007596:Joints / Q000276:immunology / Q000473:pathology; D007794:Lameness, Animal / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D012756:Sheep; D018709:Statistics, Nonparametric; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D024043:Collagen Type II; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1
Histopathological scoring; Lymphocytes; Ovine; Rheumatoid arthritis; Synovium