Establishment Of An Osteoarthritis Model Induced By Advanced Glycation End Products Accumulation And Pioglitazone Intervention Study

Objective:Explore the methods of establish an osteoarthritis rabbit model induced by the injection of D-ribose combined with exercise load, To investigate the influence of advanced glycation end products accumulation in cartilage and determine the protective effects of pioglitazone.Design:1. The New Zealand white rabbit was as the research object, eight rabbits breeding freely and measure the average daily activity S, through the video monitoring and recording trajectory method; 2. Thirty-two rabbits were separated into 4 groups randomly (n= 8 each), In order to increase exercise load, all the rabbits ran 6S on treadmills every day, and received 500 ?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 for seven weeks. Cartilage damage was evaluated macroscopically, histologically, and biochemically; 3. Another 16 rabbits ran 6S on treadmills every day and divided into 2 groups (n= 8), the two groups were administered 1000 mmol/L D-ribose that received either placebo or pioglitazone administered orally at 20 mg/kg/day for seven weeks. Then, cartilage damage was evaluated macroscopically, histologically, and biochemically.Results:1. Rabbit average daily movement distance is about 50 meters.2. Artificially increasing the AGEs level and exercise load resulted in cartilage damage, increased the expression of MMP-13 and TNF-a, and dose-dependent downregulation of PPARy expression.3. 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:1. Intra-articular injection of D-ribose combined with exercise load can increase the concentration of AGEs in articular cartilage and synovial fluid, and simulate joint AGEs accumulation; 2. Elevating AGEs in rabbits can accelerate the articular cartilage degradation, increase the expression of MMP-13 and TNF-a, and downregulate PPARy expression that occurs with daily physical exercise of 300 meters; 3. Pioglitazone can reduce the severity of the AGEs-induced OA in a rabbit model and the AGEs induced expression of MMP-13 and TNF-a in articular cartilage and synovial fluid.