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

Summary 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-γ (PPARγ) 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 μL 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 PPARγ 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.