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

Brian C. Hanks DVM1, Keichi Kuroki DVM, PhD1, Aaron M. Stoker PhD1, and James L. Cook DVM, PhD1
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  • 1 Comparative Orthopaedic Laboratory, Department of Veterinary Pathobiology College of Veterinary Medicine, University of Missouri, Columbia, MO 65211.

Abstract

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)-1β (positive control) or with IL-1β and 2 concentrations of 2 PPARγ agonists (15-deoxy-Δ 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-1β (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 (Am J Vet Res 2010;71:1142-1147)

Contributor Notes

Dr. Hanks' present address is Sinclair Research Center LLC, 562 State Rd DD, Auxvasse, MO 65231.

Support for Dr. Hanks was provided by NIH grant No. T32 RR007004.

Address correspondence to Dr. Hanks (chanks@sinclairresearch.com).