Glucocorticoids inhibit bone resorption by isolated rat osteoclasts by enhancing apoptosis.
We have studied the effects of glucocorticoids on the activity and viability of neonatal rat osteoclasts in vitro. In the bone slice assay, glucocorticoids caused a dose-dependent decrease in the amount of bone resorbed, which was accompanied by a parallel decrease in osteoclast number. Loss of osteoclasts was due to their death, which occurred by the process of apoptosis. Evidence for the latter was obtained by a range of techniques, including time-lapse video microscopy, acridine orange staining, DNA fragment detection and transmission electron microscopy. Immunocytochemistry revealed the presence of glucocorticoid receptors in osteoclasts, and glucocorticoid-induced cell death could be prevented by the glucocorticoid receptor antagonist, RU486. These observations suggest that glucocorticoids promote receptor-mediated apoptosis of rat osteoclasts in vitro. This finding may help to explain recent data indicating that, in sharp contrast with their effects on the human skeleton, glucocorticoids inhibit bone resorption and increase bone mass in rats in vivo.
Dempster
D W
DW
Regional Bone Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw 10993, USA.
Moonga
B S
BS
Stein
L S
LS
Horbert
W R
WR
Antakly
T
T
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D002452:Cell Count; D002478:Cells, Cultured; D003345:Corticosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008854:Microscopy, Electron; D015735:Mifepristone / Q000494:pharmacology; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical
D000893:Anti-Inflammatory Agents; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D003345:Corticosterone