PROSTACYCLIN (PGI(2)) - A POTENTIAL MEDIATOR OF C-FOS EXPRESSION INDUCED BY HYDROSTATIC-PRESSURE IN OSTEOBLASTIC CELLS

Application of compressive forces to osteoblastic cells is known to ca use specific cellular responses. We report that hydrostatic pressure i ncreased c-fos mRNA expression in MC3T3-E1 cells after 15, 30 and 60 m in. This effect was absent when 5 x 10(-7) mol L(-1) indomethacin, an inhibitor of prostaglandin synthesis, was present in the culture mediu m during pressurization. Using radioimmunoassays, a significant increa se in the concentrations of 6-keto-PGF(1 alpha), the stable conversion product of prostacyclin (PGI(2)), in the conditioned medium of pressu rized cells, was measured after 60 min. In contrast, PGE(2) levels wer e not significantly changed and we therefore assume that under these e xperimental conditions PGE(2) is not responsible for the transduction of the hydrostatic force. However, we also found that PGE(2) has the c apacity to induce c-fos mRNA in MC3T3-E1 cells. Furthermore, we show f or the first time that the stable prostacyclin analogue, Iloprost-Trom etamol (Ilomedin), is a potent activator of c-fos gene transcription. Our data suggest that prostacyclin is a likely candidate in mediating the effect of hydrostatic compressive stress on bone cells by regulati ng the level of c-fos mRNA, a member of the activator protein (AP)-1 c omplex and potent regulator of osteoblastic proliferation and differen tiation.