Abstract | OBJECTIVE: 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. RESULTS:
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.
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Authors | Maxim Moreau, Christelle Boileau, Johanne Martel-Pelletier, Julie Brunet, Stefan Laufer, Jean-Pierre Pelletier |
Journal | The Journal of rheumatology
(J Rheumatol)
Vol. 33
Issue 6
Pg. 1176-83
(Jun 2006)
ISSN: 0315-162X [Print] Canada |
PMID | 16652435
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Acetates
- Enzyme Inhibitors
- Pyrroles
- Metalloproteases
- Collagenases
- licofelone
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Topics |
- Acetates
(therapeutic use)
- Animals
- Anterior Cruciate Ligament
(surgery)
- Cartilage, Articular
(drug effects, enzymology, pathology)
- Collagenases
(metabolism)
- Disease Models, Animal
- Disease Progression
- Dogs
- Enzyme Inhibitors
(therapeutic use)
- Metalloproteases
(genetics, metabolism)
- Osteoarthritis, Knee
(drug therapy, metabolism, pathology)
- Pyrroles
(therapeutic use)
- Stifle
(surgery)
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