Effects of arachidonic acid metabolites on the bone metabolism

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Cultured osteoblast-like cells (MC3T3-E1) isolated from mouse calvaria have been recognized to retain their unique properties of initiating mineralization. Therefore, the cells have been used as a good model for studing bone formation in vitro. Since 3T3-E1 cells have a high capacity for prostaglandin E_2 (PGE_2) synthesis, we studied the effects of PGE_2 on the phenotype of osteoblasts. in the early stage of culture, indomethacin suppressed the proliferation and an addition of PGE_2 stimultes it. In the lasts stage of the culture, the cells were differentiated to osteocytes and mineralized. In this stage, PGE_2 synthesis was down to 10% compared with that in the early stage. If the PGE_2 synthesis was blocked by indomethacin, the appearance of the mineral deposit was stimulated. On the contrary, the addition of PGE_2 suppressed the mineralization completely.Next, we examined the effect of PGE_2 on osteoclast-like cell formation using mouse bone marrow culture system. PGE_2 stimulated the formation of multi-nucleated osteoclasts in this system. The site of the stimulation by PGE_2 is thought to be promoting the differentiation from monocytes to tartrate-resistant acid phosphatase stained cells in the step-wise treatment of PGE_2. It is well-known that PGE_2 is a potent bone resobing factor, while there are reports that PGE_2 induced contraction in isolated osteoclasts, resulting in suppression of bone resorption. In our experiment, we demonstrate that PGE_2 produced by osteoblasts stimulated both proliferation and the recruitment of osteoclasts. however, in the last stage of bone recruitment PGE_2 inhibited both mineralization and bone resorption.These data suggest that PGE_2 is the very important autacoid in bone metabolism.