RT Journal Article
SR Electronic
T1 Licofelone reduces progression of structural changes in a canine model of osteoarthritis under curative conditions: effect on protease expression and activity.
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1176
OP 1183
VO 33
IS 6
A1 Maxim Moreau
A1 Christelle Boileau
A1 Johanne Martel-Pelletier
A1 Julie Brunet
A1 Stefan Laufer
A1 Jean-Pierre Pelletier
YR 2006
UL http://www.jrheum.org/content/33/6/1176.abstract
AB OBJECTIVE: We investigated the effectiveness of licofelone, a combined 5-lipoxygenase and cyclooxygenase inhibitor, on structural changes in the anterior cruciate ligament (ACL) experimental dog model of osteoarthritis (OA) under therapeutic conditions. The effect of drug treatment on the expression and activity of metalloproteases in the OA cartilage was also studied. METHODS: The cranial cruciate ligament of the right stifle joint was surgically sectioned in 14 dogs to create OA lesions. Of these dogs, 7 received placebo treatment and served as OA controls, while 7 were treated with licofelone 2.5 mg/kg twice daily for an 8-week period, starting 4 weeks after surgery. At necropsy, macroscopic evaluations were made of the size of osteophytes and the severity of cartilage lesions on femoral condyles and tibial plateaus. Collagenase and other metalloprotease activity levels in cartilage were measured. Levels of gene expression of matrix metalloprotease (MMP-1), MMP-13, cathepsin K, and ADAMTS-5 were quantified by RT-PCR. RESUTLS: Licofelone treatment reduced the development of osteophytes and size of cartilage lesions on the femoral condyles and on the tibial plateaus (p < 0.04). Drug treatment also significantly decreased collagenase (p < 0.02) and metalloprotease (p < 0.04) activities, as well as the levels of gene expression of MMP-1 (p < 0.01), MMP-13 (p < 0.05), cathepsin K, and ADAMTS-5 (p = 0.01). CONCLUSION: Under therapeutic conditions licofelone showed the ability to reduce the progression of structural changes in experimental dog OA. This beneficial effect is likely mediated through decrease in the synthesis of a number of catabolic factors, including proteolytic enzymes, involved in cartilage breakdown.