17 beta-estradiol induces apoptosis in the preosteoclastic FLG 29.1 cell line

Although compelling data have demonstrated the effectiveness of estrogen re placement therapy for the treatment of accelerated bone loss in postmenopau sal osteoporosis and ovariectomized animals, the mechanisms by which estrog ens reduce bone resorption remain to be elucidated. To address this issue, in the present study we investigated whether estrogens were able to induce programmed cell death or apoptosis in osteoclast precursors. To this purpos e, a preosteoclastic cell line (FLG 29.1) was cultured in the absence or pr esence of nanomolar concentrations of 17 beta-estradiol (17 beta E-2). Usin g time-lapse videomicroscopy, it was shown that 17 beta E-2 induced FLG 29. 1 cell apoptosis in a dose- and time-dependent manner. Furthermore, a signi ficant increase in the activity of caspase 3 enzyme and in the number of nu clei undergoing DNA fragmentation was observed in FLG 29.1 cells treated wi th 17 beta E-2 compared to untreated cells. Finally, transmission electron microscopy of the treated cells showed typical apoptotic morphology. These data indicate that 17 beta E-2 is able to promote in vitro apoptosis in pre osteoclastic cells and suggest that estrogenic molecules may exert in vivo a direct role in negatively modulating the pool of undifferentiated bone ma rrow cells capable ultimately of maturing into osteoclasts. (C) 1999 Academ ic Press.