Subchondral and trabecular bone metabolism regulation in canine experimental knee osteoarthritis

Objective: To determine trabecular and subchondral bone metabolic changes in experimental canine osteoarthritis (OA). Methods: OA was induced in 19 dogs by transection of the anterior cruciate ligament (ACL) of the right knee through a stab wound. Dogs were sacrificed at 8 (n = 7) and 12 weeks (n = 12) after surgery. Non-operated normal dogs (n = 6) were used as controls. After sacrifice, samples were obtained from the weight-bearing area of medial tibial plateaus. Explants and cell cultures were prepared from subchondral and trabecular bone. Osteocalcin (Oc), cellular alkaline phosphatase (ALPase), urokinase plasminogen-activator (uPA), prostaglandin E-2 (PGE(2)), metalloproteinase (MMP) and nitric oxide (NO) were measured using standard procedures. Results: ALPase production was significantly increased only at week 12 in subchondral and trabecular bone, while an increase in Oc was noted at week 8. uPA and MMP activity were increased significantly at week 12 in subchondral bone, while PGE(2) levels were significantly higher in subchondral and trabecular bone at week 12 compared to normal. A decrease in NO production appeared late at week 12 in trabecular bone, whereas NO levels from subchondral bone were significantly increased compared to normal at week 8. Discussion: Intense bone remodeling takes place in both subchondral and trabecular bone in the knee following ACL transection. This process seems to occur around week 12, although Oc and NO appeared to be involved earlier at 8 weeks. These results suggest that not only subchondral but also trabecular bone metabolism is altered in this CA model. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.