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

Osteoarthritis Cartilage. 2016 Feb;24(2):307-14. doi: 10.1016/j.joca.2015.08.001. Epub 2015 Aug 29.

Abstract

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.

Keywords: Advanced glycation end products (AGEs); Animal model; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Disease Models, Animal
  • Glycation End Products, Advanced / drug effects*
  • Glycation End Products, Advanced / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Injections, Intra-Articular
  • Osteoarthritis, Knee / metabolism*
  • Osteoarthritis, Knee / pathology
  • PPAR gamma / agonists
  • Pioglitazone
  • Rabbits
  • Stifle / drug effects*
  • Stifle / metabolism
  • Stifle / pathology
  • Thiazolidinediones / pharmacology*

Substances

  • Glycation End Products, Advanced
  • Hypoglycemic Agents
  • PPAR gamma
  • Thiazolidinediones
  • Pioglitazone