Evaluation of anti-inflammatory and chondroprotective effects of peroxisome proliferator-activated receptor gamma agonists in cartilage and synovial explants from dogs.

OBJECTIVE: To evaluate the effects of peroxisome proliferator-activated receptor gamma (PPARγ) agonists on tissue metabolism in cartilage and synovial explants from dogs. SAMPLE POPULATION: Cartilage-synovial membrane expiants from 12 dogs. PROCEDURES: Expiants were cultured for 21 days without (negative control) or with interleukin (IL)-1beta (positive control) or with IL-1beta and 2 concentrations of 2 PPARγ agonists (15-deoxy-Delta 12,14-prostaglandin J2 [PGJ2] and pioglitazone). Media were collected on days 3, 7, 9, 12, 15, 18, and 21 and assessed for glycosaminoglycan (GAG), nitric oxide (NO), and prostaglandin E2 (PGE2) concentrations. Tissue GAG and hydroxyproline concentrations were determined in cartilage expiants collected on day 21.
RESULTS: The GAG concentrations of cartilage expiants cultured in IL-1beta (100 ng/mL) with 2 concentrations of PGJ2 were significantly higher than those in all other groups, whereas media GAG concentrations were significantly lower in the high-concentration PGJ2-treated groups, compared with all other groups. The PGE2 concentrations were significantly lower in the PGJ2 treatment groups, compared with the positive control and the pioglitazone treatment groups on days 3 to 21. The NO concentrations were significantly lower in PGJ2 treatment groups, compared with the other groups on days 3 and 12 to 21. CONCLUSIONS AND CLINICAL RELEVANCE: PGJ2, an endogenous PPARγ agonist, may have anti-inflammatory and chondroprotective effects in an osteosteoarthritic joint environment.