Establishment of a rabbit model to study the influence of advanced glycation end products accumulation on osteoarthritis and the protective effect of pioglitazone

Objective: To investigate the role of advanced glycation end products (AGEs) in cartilage degeneration in vivo and determine the influence of the peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist pioglitazone on AGEs-induced osteoarthritis (OA) in a rabbit model. Design: Thirty-two rabbits were separated into four groups (n = 8 each) and received 500 mu L of 123, 350, or 1000 mmol/L D-ribose or Phosphate buffered saline (PBS) solution administered to the right stifle joint via intra-articular injection twice a week. All the rabbits ran 500 m on treadmills every day. Another 16 rabbits were administered 1000 mmol/L D-ribose and divided into 2 groups (n = 8) that received either placebo or pioglitazone administered orally at 20 mg/kg/day. Eight weeks later, cartilage damage was evaluated macroscopically, histologically, and biochemically. Results: Artificially increasing the AGEs level and exercise load resulted in cartilage damage and dose-dependent downregulation of PPAR gamma expression. The efficacy of pioglitazone treatment was tested in a rabbit OA model, and a clear chondroprotective effect was revealed by macro- and microscopic assessments. Conclusion: Elevating AGEs in rabbits can accelerate the articular cartilage degradation that occurs with physical exercise, and pioglitazone can reduce the severity of the AGEs-induced OA in a rabbit model. (C) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.