Glucocorticoid-induced
osteoporosis may be at least in part due to the increased apoptosis of osteocytes. To study the role of osteocyte apoptosis in
glucocorticoid-induced
osteoporosis, we isolated primary osteocytes from murine calvaria for the analysis of the effects of
dexamethasone in in vitro culture. The cells were identified by morphology, cytochemical staining, immunocytochemical staining and
mRNA expression of
phosphate-regulating gene with homology to
endopeptidases on the X chromosome (PHEX) and
sclerosteosis/
van Buchem disease gene (SOST). We found that
dexamethasone induced osteocyte apoptosis in a dose-dependent manner. A
glucocorticoid receptor antagonist,
mifepristone (
RU486), suppressed
dexamethasone-induced osteocyte apoptosis, suggesting that it was mediated by
glucocorticoid receptor. Immunocytochemical stainings showed that
glucocorticoid receptors are present in primary osteocytes, and they were translocated to nuclei after the exposure to
dexamethasone. Addition of
estrogen prevented
glucocorticoid receptor translocation into nuclei. Corresponding antiapoptotic effects in primary osteocytes were also seen after the pretreatment of primary osteocytes with a picomolar concentration of
estrogen. The pure
antiestrogen ICI 182,780 inhibited
estrogen effect on apoptosis induced by
dexamethasone. These data suggest that
glucocorticoid receptors play an important role in
glucocorticoid-induced osteocyte apoptosis. Most importantly,
estrogen has a protective effect against osteocyte apoptosis. To conclude, the mechanism of
glucocorticoid-induced
osteoporosis may be due to the apoptosis of osteocytes, which can be opposed by
estrogen.