17beta-estradiol induces apoptosis in the preosteoclastic FLG 29.1 cell line.
Although compelling data have demonstrated the effectiveness of estrogen replacement therapy for the treatment of accelerated bone loss in postmenopausal osteoporosis and ovariectomized animals, the mechanisms by which estrogens 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 purpose, a preosteoclastic cell line (FLG 29.1) was cultured in the absence or presence of nanomolar concentrations of 17beta-estradiol (17betaE2). Using time-lapse videomicroscopy, it was shown that 17betaE2 induced FLG 29.1 cell apoptosis in a dose- and time-dependent manner. Furthermore, a significant increase in the activity of caspase 3 enzyme and in the number of nuclei undergoing DNA fragmentation was observed in FLG 29.1 cells treated with 17betaE2 compared to untreated cells. Finally, transmission electron microscopy of the treated cells showed typical apoptotic morphology. These data indicate that 17betaE2 is able to promote in vitro apoptosis in preosteoclastic cells and suggest that estrogenic molecules may exert in vivo a direct role in negatively modulating the pool of undifferentiated bone marrow cells capable ultimately of maturing into osteoclasts.
Department of Human Anatomy and Histology, University of Florence, Florence, Italy.
S
S
Zecchi-Orlandini
L
L
Formigli
A
A
Tani
S
S
Benvenuti
G
G
Fiorelli
L
L
Papucci
S
S
Capaccioli
G E
GE
Orlandini
M L
ML
Brandi
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000648:ultrastructure; D053938:DNA Fragmentation; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D000091344:Filaggrin Proteins; D005453:Fluorescence; D006801:Humans; D008854:Microscopy, Electron; D018715:Microscopy, Video; D010010:Osteoclasts / Q000187:drug effects*; D013997:Time Factors
C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D004958:Estradiol; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases