Female estrogen receptor beta-/- mice are partially protected against age-related trabecular bone loss

Citation
Sh. Windahl et al., Female estrogen receptor beta-/- mice are partially protected against age-related trabecular bone loss, J BONE MIN, 16(8), 2001, pp. 1388-1398
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF BONE AND MINERAL RESEARCH
ISSN journal
0884-0431 → ACNP
Volume
16
Issue
8
Year of publication
2001
Pages
1388 - 1398
Database
ISI
SICI code
0884-0431(200108)16:8<1388:FERBMA>2.0.ZU;2-3
Abstract
Recently, it has been shown that inactivation of estrogen receptor beta (ER -beta) by gene targeting results in increased cortical bone formation in ad olescent female mice. To study the possible involvement of ER-beta in the r egulation of the mature skeleton, we have extended the analyses to include 1-year-old ER-beta knockout mice (ER-beta-/-). Male ER-beta-/- mice did not express any significant bone phenotypic alterations at this developmental stage. However, the increase in cortical bone parameters seen already in th e adolescent female ER-beta-/- mice was maintained in the older females. Th e aged female ER-beta-/- mice further exhibited a significantly higher trab ecular bone mineral density (BMD) as well as increased bone volume/total vo lume (BV/TV) compared with wild-type (wt) mice. This was caused by a less p ronounced loss of trabecular bone during adulthood in female ER-beta-/- mic e. The growth plate width was unaltered in the female ER-beta-/- mice. Judg ed by the expression of the osteoclast marker tartrate-resistant acid phosp hatase (TRAP) and cathepsin K (cat K; reverse-transcription-polymerase chai n reaction [RT-PCR]) as well as the serum levels of C-terminal type I colla gen cross-linked peptide, bone resorption appeared unaffected. However, an increase in the messenger RNA (mRNA) expression levels of the osteoblast ma rker core-binding factor alpha1 (Cbfa1) suggested an anabolic effect in bon es of old female ER-beta-/- mice. In addition, the mRNA expression of ER-a was augmented, indicating a role for ER-alpha in the development of this ph enotype. Taken together, the results show that ER-beta is involved in the r egulation of trabecular bone during adulthood in female mice and suggest th at ER-beta acts in a repressive manner, possibly by counteracting the stimu latory action of ER-alpha on bone formation.