Modulation of osteoblast function by prostaglandins

D. T. Yamaguchi, J. Green, B. S. Merritt, C. R. Kleeman and S. Muallem Laboratory of Membrane Biology, Cedars-Sinai Medical Center, Los Angeles 90048. The naturally occurring prostaglandins (PGs) were studied with respect to their abilities to change free cytosolic Ca2+ concentrations ([Ca2+]i), adenosine 3',5'-cyclic monophosphate (cAMP) levels, and cell proliferation in the osteoblastic cell line, UMR-106-01, and primary cultures of osteoblasts prepared from neonatal rat calvariae. All PGs tested stimulated an increase in [Ca2+]i, which was mainly due to Ca2+ release from intracellular stores. Measurements of the 50% effective concentration for the different PGs show that the potency ranking for PG-evoked [Ca2+]i increase in these cells is F2 alpha greater than D2 much greater than E2 greater than TxB2 greater than E1 greater than I2 much greater than A2. The PGs also increase cAMP levels in osteoblasts. At the highest concentrations tested (10-25 microM), dose-response saturation of cAMP production was observed only by PGE2 and PGE1. The potency rank for PG-stimulated cAMP increase was E2 greater than E1 much greater than A2 greater than I2 greater than F2 alpha greater than D2 greater than TxB2. Measurements of the effect of the PGs on thymidine uptake showed that low concentrations of PGF2 alpha and PGD2 had either no effect or stimulated proliferation of osteoblast-like cells. Relatively low concentration of PGE2, PGE1, and PGA2 inhibited proliferation. The potency ranking for PG-mediated inhibition of cell proliferation was identical to that found for PG-stimulated cAMP production. We conclude that all the naturally occurring PGs tested can activate the two signal transduction systems in osteoblasts.