Evidence to suggest that cathepsin K degrades articular cartilage in naturally occurring equine osteoarthritis.
OBJECTIVE
The mechanisms leading to degeneration of articular cartilage in osteoarthritis (OA) are complex and not yet fully understood. Cathepsin K (CK) is a cysteine protease which can also cleave the triple helix of type II collagen. This exposes a neoepitope that can now be identified by specific antibodies. The aim of this study was to obtain evidence suggesting a role for CK in naturally occurring equine OA in both lesional and peri-lesional regions.


METHODS
Articular cartilages (n=12 horses; 5 healthy, 7 OA) were harvested from animals postmortem. A gross macroscopic examination, histologic (Safranin O-Fast Green and Picrosirius red staining) and immunohistochemical evaluation were performed. Samples were divided into normal appearing cartilage, peri-lesional and lesional cartilage. Cartilage degradation in the samples was graded histologically and immunohistochemically. CK and possible CK cleavage were detected immunohistochemically with specific anti-protein and anti-neoepitope antibodies, respectively. A comparison of CK neoepitope (C2K) production with the collagenase-generated neoepitope produced by matrix metalloproteinases (MMP)-1, 8 and 13 (C2C) was also assessed immunohistochemically.


RESULTS
CK and CK cleavage were significantly more abundant in OA cartilage (both peri-lesional and lesional) when compared to remote cartilage within the sample joint or cartilage from healthy joints. The immunohistochemical pattern observed for CK degradation (C2K) was similar to that of collagenase degradation (C2C). Macroscopic cartilage changes and histologic findings were significantly correlated with immunohistochemistry results.


CONCLUSIONS
The data generated suggests that CK may be involved in cartilage collagen degradation in naturally occurring osteoarthritis.
Vinardell
T
T
Département des sciences cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Québec, Canada.
Dejica
V
V
Poole
A R
AR
Mort
J S
JS
Richard
H
H
Laverty
S
S
D000818:Animals; D002350:Carpus, Animal; D002358:Cartilage, Articular / Q000201:enzymology* / Q000473:pathology; D056657:Cathepsin K; D002403:Cathepsins / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D017364:Collagenases / Q000378:metabolism; D000939:Epitopes / Q000032:analysis; D005260:Female; D006734:Horse Diseases / Q000201:enzymology* / Q000473:pathology; D006736:Horses; D008297:Male; D010003:Osteoarthritis / Q000201:enzymology*; D013194:Staining and Labeling
D024043:Collagen Type II; D000939:Epitopes; D002403:Cathepsins; D056657:Cathepsin K; D017364:Collagenases