Effect of glucocorticoid on prostaglandin F(2α)-induced prostaglandin E₂ synthesis in osteoblast-like cells: Inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A₂

It is well known that osteoporosis is a common complication of patients with glucocorticoid excess. We showed previously that prostaglandin (PG) F(2α), stimulates the synthesis of PGE₂, a potent bone resorbing agent, and that the activation of protein kinase C amplifies the PGF(2α)-induced PGE₂ synthesis through the potentiation of phospholipase A₂ activity in osteoblast-like MC3T3-E1 cells. In the present;study, we examined the effect of dexamethasone on PGE₂ synthesis induced by PGF(2α), in MC3T3-E1 cells. The pretreatment with dexamethasone significantly inhibited the PGE₂ synthesis in a dose-dependent manner in the range between 0.1 and 10 nmol/l in these cells. This effect of dexamethasone was dependent on the time of pretreatment up to 8 h. Dexamethasone also inhibited PGE₂ synthesis induced by melittin, known as a phospholipase A₂ activator. Furthermore, dexamethasone significantly inhibited the enhancement of PGF(2α)- or melittin-induced PGE₂ synthesis by 12-O-tetradecanoylphorbol-13-acetate, known as a protein kinase C activator. In addition, dexamethasone significantly inhibited PGF(2α)-induced formation of inositol phosphates in a dose-dependent manner between 0.1 and 10 nmol/l in MC3T3-E1 cells. These results strongly suggest that glucocorticoid inhibits PGF(2α)-induced PGE₂ synthesis through the inhibition of phosphoinositide hydrolysis by phospholipase C as well as phospholipase A₂ in osteoblast-like cells.