title: Carprofen simultaneously reduces progression of morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis.
abstract: OBJECTIVE
  To examine the effect of a nonsteroidal antiinflammatory drug, carprofen, on the structure and metabolism of cartilage and subchondral bone in the experimental osteoarthritic (OA) canine model.
  
  
  METHODS
  Experimental Groups 1 and 2 received a sectioning of the anterior cruciate ligament (ACL) of the right stifle joint, and were administered carprofen (2.2 and 4.4 mg/kg/twice daily/po, respectively) for 8 weeks beginning 4 weeks postsurgery. Group 3 received ACL sectioning and no treatment. Group 4 was composed of unoperated normal dogs. Cartilage macroscopic lesions were assessed, and their histological severity was graded. Specimens of subchondral bones were fixed, decalcified, and stained with hematoxylin/eosin. The level of metalloprotease (MMP) activity in cartilage was measured. Osteoblast cells were prepared from the subchondral bone. The level of synthesis of osteoblast biomarkers (osteocalcin, alkaline phosphatase), as well as urokinase plasminogen activator (uPA) activity and insulin-like growth factor (IGF-1) in the culture medium, was estimated.
  
  
  RESULTS
  Carprofen treatment decreased the width of osteophytes (p < 0.01), the size of cartilage lesions, and the histologic severity of cartilage lesions (p < 0.008). There was no difference in the levels of MMP activity in cartilage between OA and carprofen treated groups. In OA dogs, the subchondral bone plate was thinner and was the site of an extensive remodeling process with numerous lacunae. Dogs treated with carprofen showed a marked decrease in the remodeling activity with normal plate thickness, and subchondral bone morphology resembling that of normal dogs. Osteoblasts from untreated OA dogs showed slightly higher alkaline phosphatase activities and osteocalcin release that reverted back to normal upon carprofen treatment. Moreover, uPA activity and IGF-1 levels were increased in OA dogs and were significantly reduced in carprofen treated dogs.
  
  
  CONCLUSIONS
  Under therapeutic conditions, treatment with carprofen could reduce the progression of early structural changes in experimental OA. Carprofen treatment also delays and/or prevents the abnormal metabolism of subchondral osteoblasts in this model. The hypothesis of a possible link between the protective effect of carprofen and its effect on subchondral bone is of interest in the context of therapeutic intervention.
authors: Osteoarthritis Research Unit, H pital Notre-Dame, Centre hospitalier de l'Université de Montréal, Québec, Canada.
authors: J P
authors: JP
authors: Pelletier
authors: D
authors: D
authors: Lajeunesse
authors: D V
authors: DV
authors: Jovanovic
authors: V
authors: V
authors: Lascau-Coman
authors: F C
authors: FC
authors: Jolicoeur
authors: G
authors: G
authors: Hilal
authors: J C
authors: JC
authors: Fernandes
authors: J
authors: J
authors: Martel-Pelletier
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002227:Carbazoles / Q000627:therapeutic use*; D002356:Cartilage / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D005260:Female; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D013583:Synovial Membrane / Q000187:drug effects / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002227:Carbazoles; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D020782:Matrix Metalloproteinases; C007005:carprofen