Treatment with licofelone prevents abnormal subchondral bone cell metabolism in experimental dog osteoarthritis.
OBJECTIVE
To determine if treatment with licofelone, a combined 5-lipoxygenase and cyclo-oxygenase inhibitor, in vivo in experimental dog osteoarthritis can modify bone cell metabolism in long term in vitro subchondral osteoblast cell cultures (Ob).


METHODS
Group 1 received sectioning of the anterior cruciate ligament (ACL) of the right knee with no active treatment (placebo group). Groups 2 and 3 received sectioning of the ACL of the right knee, and were given licofelone (2.5 or 5.0 mg/kg daily by mouth, respectively) for eight weeks beginning the day after surgery. Primary Ob were prepared from the subchondral bone plate. Levels of phenotypic markers (alkaline phosphatase activity, osteocalcin release), and urokinase plasminogen activator (uPA) and insulin-like growth factor-1 (IGF-I) levels, were evaluated in each group. Lastly, prostaglandin E(2) (PGE(2)) and leucotriene B(4) levels were evaluated.


RESULTS
No significant differences in alkaline phosphatase activity or osteocalcin release from Ob between the three groups, under either basal or 1,25(OH)(2)D(3) induction were seen. In contrast, treatment with licofelone reduced uPA and IGF-I levels in Ob. PGE(2) levels, which were still raised in the placebo group, were decreased sharply by licofelone. A relationship was found between licofelone treatment and either the reduction in the size of lesions on tibial plateaus or the levels of uPA, IGF-I, or PGE(2).


CONCLUSIONS
Licofelone treatment prevents and/or delays the abnormal metabolism of subchondral osteoblasts in this model. Licofelone reduced PGE(2) levels after long term Ob, suggesting that the reduction in uPA and IGF-I levels is linked, at least in part, to this reduction.
Lajeunesse
D
D
Unité de recherche en Arthrose, Centre Hospitalier de l'Université de Montréal, Hôpital Notre-Dame, Montréal, Québec, Canada. lajeunda@jonction.net
Martel-Pelletier
J
J
Fernandes
J C
JC
Laufer
S
S
Pelletier
J-P
JP
D000085:Acetates / Q000627:therapeutic use*; D000818:Animals; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004285:Dogs; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000085:Acetates; D018501:Antirheumatic Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; D007975:Leukotriene B4; D007334:Insulin-Like Growth Factor I; D014568:Urokinase-Type Plasminogen Activator; D015232:Dinoprostone; C088092:licofelone