Inhibition of COX-2 by celecoxib in the canine groove model of osteoarthritis.
OBJECTIVE
In vitro studies showed a beneficial effect of celecoxib on proteoglycan turnover and content of osteoarthritic cartilage. In the present study we evaluated whether these favourable effects of celecoxib could also be demonstrated in vivo.


METHODS
In 24 Beagle dogs, osteoarthritis (OA) was induced in one knee according to the groove model. The animals were divided into three groups and received oral placebo or 100 or 200 mg celecoxib daily, starting directly after surgery. After 15 weeks joint tissue from all dogs was analysed.


RESULTS
Induction of OA resulted in macroscopic and histological damage of cartilage, changes in cartilage proteoglycan turnover, loss of cartilage matrix proteoglycans and slight synovial inflammation, all characteristic of early OA. Surprisingly, none of the parameters was significantly changed upon celecoxib treatment. Synovial fluid prostaglandin E(2) levels were dose-dependently diminished by celecoxib, demonstrating that the celecoxib had reached the joint in sufficient amounts. Using an in vitro setup, canine cartilage under degenerative conditions was favourably influenced by celecoxib, demonstrating that canine cartilage is sensitive to celecoxib.


CONCLUSIONS
The present study showed a chondroneutral effect of celecoxib on the characteristics of experimentally induced OA in vivo, in contrast to the observed beneficial effect in vitro. It could be that celecoxib had been beneficial to degenerated cartilage in vivo but that these effects were counteracted by increased loading of the affected joint and the associated progression of OA, occurring because of the well-known analgesic effects of celecoxib.
Mastbergen
S C
SC
Rheumatology and Clinical Immunology, University Medical Center Utrecht, PO Box 85500 (F02.127), 3508 GA Utrecht, The Netherlands. S.Mastbergen@azu.nl
Marijnissen
A C
AC
Vianen
M E
ME
Zoer
B
B
van Roermund
P M
PM
Bijlsma
J W
JW
Lafeber
F P
FP
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006614:Hindlimb; D010003:Osteoarthritis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism; D011720:Pyrazoles / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D013582:Synovial Fluid / Q000378:metabolism; D013585:Synovitis / Q000150:complications / Q000188:drug therapy / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011509:Proteoglycans; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone