Effects of leukotrienes on osteoblastic cell proliferation

Leukeotriene B₄ (LTB₄) is an arachidonic acid lipoxygenase metabolite with well-characterized effects on leukocytes. LTB₄ has been implicated in acute inflammatory reactions and in bone resorption. In the present study, the effect of LTB₄ on osteoblastic cells was examined. LTB₄ inhibited cell proliferation in normal osteoblastic rat calvaria cells in a dose-dependent manner and had biphasic effects in the human osteoblast-like osteosarcoma cell lines Saos-2 and G292. Indomethacin did not modulate the nature of these LTB₄ effects in any of the cells. However, it potentiated the high LTB₄ dose effects in normal cells and G292 cells. AA861, an inhibitor of lipoxygenase, did not modulate the LTB₄ effects in these two cell lines. These results suggest that LTB₄ is involved in the regulation of osteoblastic cell proliferation and may interact with prostaglandins to modulate these effects.