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.
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.
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.
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.