Comparison of collagenase-cleaved articular cartilage collagen in mice in the naturally occurring STR/ort model of osteoarthritis and in collagen-induced arthritis.
OBJECTIVE
The STR/ort mouse develops a naturally occurring osteoarthritis of the femorotibial joint that provides a model with which to establish the time course of biochemical changes taking place in articular cartilage in the disease. Our objective was to define the onset, location and progression of type II collagen cleavage by collagenase in the tibial cartilage of the STR/ort mouse. For comparison, cartilage collagen cleavage was also studied in collagen-induced arthritis in DBA mice.


METHODS
STR and control CBA mice aged 6-45 weeks were examined. DBA/1 mice were studied 2 and 3 weeks after initiating collagen-induced arthritis. Collagen cleavage was detected by immunolocalization using the antibody COL2-3/4Cshort which recognizes a carboxy terminal neoepitope created by collagenase cleavage of type I and II collagens.


RESULTS
No COL 2-3/4Cshort immunostaining was observed in the intact cartilage of healthy young or old mice. The earliest detectable collagen degradation occurred at the cartilage surface coincident with the appearance of surface roughening. As fibrillations developed, further collagen degradation was evident around the edge of the lesion and in adjacent extracellular matrix. In contrast, staining was observed throughout the cartilage matrix in type II collagen-induced arthritis prior to the development of histopathological lesions.


CONCLUSIONS
No evidence was found for collagen cleavage in intact/pre-lesional cartilage from STR/ort mice. Local collagen cleavage was, however, clearly associated with very early histopathological lesions and immunostaining with COL 2-3/4Cshort increased with progression of the latter. In contrast, type II collagen cleavage occurs throughout the articular cartilage at an early stage in collagen-induced arthritis.
Price
J S
JS
Cell and Molecular Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, Sir Alexander Fleming Building, Exhibition Road, London SW7 2AZ, UK.
Chambers
M G
MG
Poole
A R
AR
Fradin
A
A
Mason
R M
RM
D000818:Animals; D001168:Arthritis / Q000201:enzymology*; D002358:Cartilage, Articular; D024043:Collagen Type II / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism*; D006614:Hindlimb; D007596:Joints; D008297:Male; D051379:Mice; D023421:Models, Animal; D010003:Osteoarthritis / Q000201:enzymology*
D024043:Collagen Type II; D017364:Collagenases