Effects of prostaglandin E2 on bone in mice in vivo

We have examined the effects of varying doses, schedules and routes of administration of prostaglandin E2 (PGE2) on bone in mice. Male C57BL/6 mice treated with a high dose of PGE2 (6 mg/kg/d) showed decreased trabecular bone volume (BV/TV) by 14 d, indicating increased bone resorption. However, there was also stimulation of bone formation at 14 d after 3 d treatment with PGE2, since mineral apposition rate (MAR) and bone formation rate (BFR/BS) were increased. In CD-1 male and female mice, PGE2 (3 mg/kg, 2/wk for 4 wk) increased MAR by 50% and BFR/BS by 100%, but there was no significant change in BV/TV. Tibial mRNA showed an increase in BMP-2 and RUNX-2 expression with PGE2. Additional experiments using a higher dose or longer exposure did not increase bone mass. We conclude that exposure to high doses of PGE2 in mice may be anabolic but is balanced by catabolic effects. Studies of PGE2 in combination with an inhibitor of resorption could lead to development of a true anabolic model and permit assessment of the roles of specific PGE2 receptors and signal transduction pathways.