Title : Expression and function of 15-prostaglandin dehydrogenase in cartilage tissue
Abstract:
Osteoarthritis (OA), among the elderly, is the most common joint disorder. It is distinguished by progressive cartilage degradation, synovitis, subchondral bone remodeling, and pain. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is responsible for the catabolism of PGE2, which has been implicated in the regulation of inflammation and cartilage biology. This study intended to evaluate the expression and function of 15-PGDH in cartilage.
Methods. The expression of 15-PGDH mRNA and protein in cartilage were analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), Immunoblotting, and immunohistochemistry, respectively. Chondrocytes were stimulated with IL-1β. The expression of 15-PGDH was evaluated by real-time RT-PCR, and western blott, and the role of 15-PGDH activity in the expression of key inflammatory and anabolic genes was evaluated using 18β-Glycyrrhetinic Acid (18 βGA), a pharmacological inhibitor of 15-PGDH activity.
Results. 15-PGDH was expressed in murine and human cartilage and its levels were lower in OA tissues suggesting that reduced levels of 15-PGDH may contribute to the development of OA. Treatment with IL-1β down-regulated the expression of 15-PGDH expression in human OA chondrocytes at the mRNA and protein levels. We also showed that treatment with 18 βGA, an inhibitor of 15-PGDH activity, up-regulated the expression of key inflammatory genes including iNOS, COX-2, and mPGES-1, and down-regulates the expression of the main anabolic genes; type II collagen and aggrecan, in cartilage.
Conclusion. Together these data suggest that 15-PGDH is involved in the pathogenesis of OA. They also suggest that targeting 15-PGDH expression and/or activity may constitute a novel anti-OA therapy involving specific modulation of PGE2 levels.
Keywords: Osteoarthritis, 15-Prostaglandine Dehydrogenase, Cartilage tissue, Prostaglandine E2, Chondrocytes, Inflammation.
