Prostaglandin E2 stimulates preosteoblast replication: an autoradiographic study in cultured fetal rat calvariae

To determine the mechanism for the anabolic effect of prostaglandins (PGs) on bone, [3H]thymidine(TdR) autoradiography was performed to localize the cells that replicate and to determine the fate of these labeled cells over time in cultured 20-day fetal rat calvariae. Treatment of bone organ cultures for 24 or 96 h with cortisol significantly decreased the number of [3H]TdR-labeled osteoblasts and periosteal cells. Treatment of bones with 0.1 or 1 microM PGE2 alone had no effect on [3H]TdR labeling of the osteoblast layer but doubled the number of labeled periosteal cells compared to control bones at 24 h. However, when both cortisol and PGE2 were added together, the number of labeled osteoblasts and periosteal cells increased. This effect was dependent on the concentration of PGE2. In bones treated with 0.1 microM PGE2 and 0.1 microM cortisol for 24 h, [3H]TdR labeling of periosteal cells was 5.5 times the labeling in bones treated with cortisol alone and osteoblast labeling increased 4.1-fold. Similar results in [3H]TdR labeling of osteoblasts and periosteal cells were found with 6-day neonatal mouse calvaria treated with PGE2 and cortisol. These data demonstrate that PGE2 in the presence of cortisol increases periosteal cell replication, which leads to an increased number of osteoblasts and increased bone formation.