Ipriflavone inhibits phosphoinositide hydrolysis and Ca²⁺ uptake in the osteoblast-like UMR-106 cells

The mechanism of action of ipriflavone, an isoflavone derivative, was studied in the osteoblastic-like UMR-106 cell line. Ipriflavone affected both phosphoinositide hydrolysis and ⁴⁵Ca²⁺ uptake. A repeated treatment of UMR-106 cells (once a day, for 3 days) with ipriflavone decreased, in a concentration-dependent manner, [³H]inositol monophosphate accumulation. This effect was also achieved single addition of high concentrations of ipriflavone or 100 nM [Asu^1,7]eel-calcitonin, a semi-synthetic analog of eel calcitonin. When repeatedly added to UMR-106 cells, 17β-estradiol produced a marked inhibition of [³H]inositol monophosphate accumulation, an effect which appeared significant only at a concentration of 1 μM and which was accompanied by a reduced incorporation of [³H]inositol into membrane phospholipids. A repeated treatment with ipriflavone reduced ⁴⁵Ca²⁺ uptake as well. This effect was observed also after a single addition of [Asu^1,7]eel-calcitonin but not following single or repeated treatment with 17β-estradiol. The present data indicate the osteoblast as a direct and specific target for ipriflavone and suggest that this compound may share intracellular transducing mechanisms with other antiosteoporotic hormones such as estrogen and calcitonin.