| Research Abstract |
Studies using a variety of in vivo and in vitro systems have indicated that osteoclast precursors are present among bone marrow cells and have suggested that osteoclasts are formed by their fusion. More recent reports arising from experiments employing long term culture of bone marrow cells state that immature monocytes may undergo fusion induced by lalpha,25-dihydroxyvitamin D_3[lalpha,25-(OH)_2D_3], resulting in multinucleated cells with several characteristics of osteoclasts. Therefore,in this study, we have developed the cell culture system to examine the mechanism of the action on bone-resorbing factor in vitro. For this purpose, we have examined separately the ability of lalpha,25-(OH)_2D_3 and the four lalpha,25-(OH)_2D_3-26,23-lactones to mediate the formation of multinucleated cells in mouse bone marrow mononuclear cell cultures. The addition of lalpha,25-(OH)_2D_3 to these cultures dose-dependently stimulated the formation of multinuleated cells over a range of lo^<-9>- lo^<-7>M.
The 23(S),25(S)- and 23(R),25(R)-lalpha,25-(OH)_2D_3-26,23-lactones also increased the number of multinucleated cells, whereas the 23(S),25(R)- and 23(R),25(S)-lalpha,25-(OH)_2D_3-26,23-lactones failed to do so. In addition, these latter two diastereoisomers inhibited the lalpha,25-(OH)_2D_3 stimulation of multinucleated cell formation, although the 23(S),25(S)- and 23(R),25(R)-lalpha,25-(OH)_2D_3-26,23-lactones did not. These multinuleated cells responded to calcitinin and contained tartrate-resistant acid phosphatase, both of which are characteristic of osteoclasts. These results suggest that the multinucleated cells formed in the mouse marrow culture satisfy most of the criteria of osteoclasts.
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