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Estrogen Prevents Glucocorticoid-Induced Apoptosis in Osteoblasts in Vivo and in Vitro1

Gohel, Anita, McCarthy, Mary-Beth, Gronowicz, Gloria·1999·Endocrinology

Abstract

The ability of estrogen to prevent glucocorticoid-induced apoptosis in osteoblasts was studied both in vitro and in vivo. Glucocorticoid treatment for 72 h produced a dose-dependent increase in the number of apoptotic cells, determined by acridine orange/ethidium bromide staining, with a maximal response of 31+/-2% and 26+/-3% with 100 nM corticosterone in primary rat and mouse osteoblasts, respectively. Simultaneous administration of varying concentrations of 17beta-estradiol and 100 nM corticosterone decreased apoptotic osteoblasts in a dose-dependent manner, with a maximal decrease of 70% with 0.01 nM 17beta-estradiol. Terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling also demonstrated glucocorticoid-induced DNA fragmentation that was inhibited by estrogen. Estrogen was shown to inhibit apoptosis induced by lipopolysaccharide treatment. As early as 6 h, Western blots demonstrated a dose-dependent decrease in the Bcl-2/Bax ratio, which reached a minimum of 0.18 in osteoblasts treated with 1000 nM corticosterone for 72 h. This reduction in Bcl-2/Bax was abolished by treating osteoblasts simultaneously with 17beta-estradiol, but not with 17alpha-estradiol. In 7-day-old mice, administration of varying concentrations of dexamethasone for 72 h resulted in a dose-dependent increase in the number of apoptotic osteoblasts as demonstrated by in situ terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling staining of calvaria. A maximum of 22+/-1% apoptotic osteoblasts on the bone surface was found with 1 mg/kg BW dexamethasone compared with 2+/-1% in vehicle-treated mice. Injection of varying concentrations of 17beta-estradiol (0.5-5 mg/kg BW), but not 17alpha-estradiol, with 1 mg/kg dexamethasone produced a dose-dependent decrease in the number of apoptotic osteoblasts to 5+/-1% with 5 mg/kg 17beta-estradiol. Thus, glucocorticoid-induced apoptosis of osteoblasts may be prevented at least in part by 17beta-estradiol.

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Metadata

Authors
Gohel, A., McCarthy, M.-B., & Gronowicz, G.
Venue
Endocrinology
Published
1999-11-01
Volume
140
Issue
11
Pages
5339-5347
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
OpenAlex
W2154012098
Cited by
244
References
5
FWCI
4.90
Type
journal article
Language
en
Open access
closed

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Gohel, A., McCarthy, M.-B., & Gronowicz, G. (1999). Estrogen Prevents Glucocorticoid-Induced Apoptosis in Osteoblasts in Vivo and in Vitro1. Endocrinology. https://doi.org/10.1210/endo.140.11.7135

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