Inhibition of myoblast migration by prostacyclin is associated with enhanced cell fusion

Satellite cells are stem cells that are critical for the formation and growth of skeletal muscle during myogenesis. To differentiate and fuse, proliferating satellite cells or myoblasts must migrate and establish stable cell-cell contacts. However, the factors that regulate myoblast migration and fusion are not understood completely. We have identified PGI(2) as a novel regulator of myogenesis in vitro. PGI(2) is a member of the family of prostaglandins ( PG), autocrine/paracrine signaling molecules synthesized via the cyclo-oxygenase-1 and -2 pathways. Primary mouse muscle cells both secrete PGI(2) and express the PGI(2) receptor, IP, at various stages of myogenesis. Using genetic and pharmacological approaches, we show that PGI(2) is a negative regulator of myoblast migration that also enhances cell fusion. Thus, PGI(2) may act as a brake on migrating cells to facilitate cell-cell contact and fusion. Together, our results highlight the importance of the balance between positive and negative regulators in cell migration and myogenesis. This work may have implications for migration of other populations of adult stem cells and/or cells that undergo fusion. Bondesen, B. A., Jones, K. A., Glasgow, W. C., Pavlath, G. K. Inhibition of myoblast migration by prostacyclin is associated with enhanced cell fusion.