Anti-inflammatory and Chondroprotective Effects of PPARγ Agonists on a Co-culture Osteoarthritis Model
Objective
To evaluate the effects of PPARγ agonists on joint health with the use of a cartilage-synovial co-culture osteoarthritis model.
Methods
We took cartilage and synovial explants from 12 dogs and co-cultured with IL-1β (inflammatory molecule).The explants were cultured for 21 days with two different concentrations of two PPARγ agonists (PGJ2 or pioglitazone) added to the liquid nutrient media. The liquid media were collected days 3, 7, 9, 12, 15, 18, and 21, and examined for glycosaminoglycan (GAG), nitric oxide (NO), and prostaglandin (PG)E2 concentrations. We then analyzed the tissue for GAG and collagen (building blocks of cartilage). Explants cultured with IL-1β (inflammatory molecule) alone served as positive control and those cultured without IL-1β or a PPARγ agonist served as negative control (non-inflammatory environment).
Results
The GAG content (per dry weight) of cartilage explants cultured in IL-1β (100ng/ml) with two different concentrations of PGJ2 were statistically higher than all other groups (p<0.05) while media GAG concentrations were statistically reduced in the high concentration PGJ2 treated groups compared to all other groups (p<0.05). PGE2 concentrations were statistically lower in the PGJ2 treatment groups compared to the positive control and the pioglitazone treatment groups (days 3-21). NO concentrations were statistically lower in PGJ2 treatment groups compared to the other groups (day 3, 12-21).
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Conclusions
These findings indicate that PGJ2, an endogenous PPAR agonist, can act as an anti-inflammatory and chondroprotective in an osteoarthritic joint environment.