Prostaglandin D2 inhibits C2C12 myogenesis

Muscle repair following injury is preceded by a rapid inflammatory response with myoblasts being exposed to high levels of prostaglandin D2 (PGD2) from invading leukocytes. We demonstrate that PGD2 strongly inhibits C2C12 myogenesis as measured by cell fusion, creatine kinase activity and MyoD, myogenin and α-actin expression. Inhibition of myogenesis required micromolar PGD2 concentrations and was independent of the known PGD2 receptors DP1 and DP2. Unlike its cyclopentenone derivative 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), PGD2 did not generate toxic mitochondrial superoxide indicating that the inhibition of myogenesis is not mediated by generation of high concentrations of PGD2-derived 15d-PGJ2. Thus our observations provide evidence for a novel PGD2 signalling mechanism during muscle repair exclusively mediated by high inflammatory associated PGD2 concentrations. These findings indicate a complex interplay between myoblasts and inflammatory cells during the repair process and have implications for the use of non-steroidal anti-inflammatory drugs in the treatment of muscle injuries.