Female estrogen receptor beta-/- mice are partially protected against age-related trabecular bone loss.
Recently, it has been shown that inactivation of estrogen receptor beta (ER-beta) by gene targeting results in increased cortical bone formation in adolescent female mice. To study the possible involvement of ER-beta in the regulation 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 the adolescent female ER-beta-/- mice was maintained in the older females. The aged female ER-beta-/- mice further exhibited a significantly higher trabecular bone mineral density (BMD) as well as increased bone volume/total volume (BV/TV) compared with wild-type (wt) mice. This was caused by a less pronounced loss of trabecular bone during adulthood in female ER-beta-/- mice. The growth plate width was unaltered in the female ER-beta-/- mice. Judged by the expression of the osteoclast marker tartrate-resistant acid phosphatase (TRAP) and cathepsin K (cat K; reverse-transcription-polymerase chain reaction [RT-PCR]) as well as the serum levels of C-terminal type I collagen cross-linked peptide, bone resorption appeared unaffected. However, an increase in the messenger RNA (mRNA) expression levels of the osteoblast marker core-binding factor alpha1 (Cbfa1) suggested an anabolic effect in bones of old female ER-beta-/- mice. In addition, the mRNA expression of ER-alpha was augmented, indicating a role for ER-alpha in the development of this phenotype. Taken together, the results show that ER-beta is involved in the regulation of trabecular bone during adulthood in female mice and suggest that ER-beta acts in a repressive manner, possibly by counteracting the stimulatory action of ER-alpha on bone formation.
Windahl
S H
SH
Department of Biosciences, Karolinska Institutet, Novum, Huddinge, Sweden.
Hollberg
K
K
Vidal
O
O
Gustafsson
J A
JA
Ohlsson
C
C
Andersson
G
G
D000818:Animals; D001835:Body Weight; D015519:Bone Density; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D003432:Cross-Linking Reagents; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D005269:Femur / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000097:blood; D010010:Osteoclasts / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D010455:Peptides / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*
D024042:Collagen Type I; D003432:Cross-Linking Reagents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010455:Peptides; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D003094:Collagen