Expression of peroxisome proliferator-activated receptors α, β, γ, and H- and L-prostaglandin D synthase during osteoarthritis in the spontaneous hartley guinea pig and experimental dog models

J Rheumatol. 2013 Jun;40(6):877-90. doi: 10.3899/jrheum.120738. Epub 2013 Apr 1.

Abstract

Objective: To investigate the expression of peroxisome proliferator-activated receptors (PPAR) α, β, and γ, and hematopoietic and lipocalin-type prostaglandin D synthase (H- and L-PGDS) over the course of osteoarthritis (OA) in the spontaneous Hartley guinea pig and the anterior cruciate ligament transection dog models.

Methods: Guinea pigs were sacrificed at 2 (control group), 4, 8, and 12 months of age (n = 5 per group). Non-operated (control) and operated dogs were sacrificed at 4, 8, and 12 weeks postsurgery. Cartilage was evaluated histologically using the Osteoarthritis Research Society International (OARSI) guidelines. The expression of PPAR-α, β, γ, and H- and L-PGDS was evaluated by real-time PCR and immunohistochemistry. The nonparametric Spearman test was used for correlation analysis.

Results: PPAR-α, β, and γ were detected in medial tibial plateau from control animals in both the spontaneous and surgical models. Levels of PPAR-α and β did not change over the course of OA, whereas PPAR-γ levels decreased during progression of disease. We also observed that the expression of H-PGDS remained unchanged, whereas L-PGDS increased over the course of OA. PPAR-γ levels correlated negatively, whereas L-PGDS levels correlated positively, with the histological score of OA.

Conclusion: The level of PPAR-γ decreased, whereas level of L-PGDS increased during the progression of OA. These data suggest that reduced expression of PPAR-γ may contribute to the pathogenesis of OA, whereas enhanced expression of L-PGDS may be part of a reparative process.

Keywords: CARTILAGE; OSTEOARTHRITIS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; PROSTAGLANDIN D SYNTHASE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / genetics
  • Arthritis, Experimental / metabolism*
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Dogs
  • Guinea Pigs
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism*
  • Knee Joint / metabolism
  • Knee Joint / pathology
  • Lipocalins / genetics
  • Lipocalins / metabolism*
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • Nitric Oxide / metabolism
  • Osteoarthritis / genetics
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Peroxisome Proliferator-Activated Receptors / genetics
  • Peroxisome Proliferator-Activated Receptors / metabolism*

Substances

  • Lipocalins
  • Peroxisome Proliferator-Activated Receptors
  • Nitric Oxide
  • Matrix Metalloproteinase 13
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase