Inactivation of estrogen receptor α in bone‐forming cells induces bone loss in female mice

The role of the estrogen receptor α (ERα) in bone‐forming cells is incompletely understood at present. To examine the in vivo effects of ERα in these cells, we generated a mouse strain in which the ERα gene is inactivated in osteoblasts via osteocalcin promoter‐regulated cyclic recombinase (Cre) act...

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Published in:The FASEB journal 2013-02, Vol.27 (2), p.478-488
Main Authors: Määttä, Jorma A., Büki, Kalman G., Gu, Guoliang, Alanne, Maria H., Vääräniemi, Jukka, Liljenbäck, Heidi, Poutanen, Matti, Härkönen, Pirkko, Väänänen, Kalervo
Format: Article
Language:English
Subjects:
Aging - metabolism
Aging - pathology
Animals
Base Sequence
Bone Development - physiology
Estrogen Receptor alpha - antagonists & inhibitors
Estrogen Receptor alpha - deficiency
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Female
Humans
Luteinizing Hormone - blood
Male
Mice
Mice, Knockout
Mice, Transgenic
osteoblast
Osteoblasts - cytology
Osteoblasts - metabolism
Osteogenesis - physiology
osteoporosis
Osteoporosis - etiology
Osteoporosis - genetics
Osteoporosis - metabolism
Phenotype
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sex Characteristics
Signal Transduction
X-Ray Microtomography
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Summary:The role of the estrogen receptor α (ERα) in bone‐forming cells is incompletely understood at present. To examine the in vivo effects of ERα in these cells, we generated a mouse strain in which the ERα gene is inactivated in osteoblasts via osteocalcin promoter‐regulated cyclic recombinase (Cre) activity (ERαΔOB/ΔOB). This enabled micro‐computed tomography‐ and histomorphometry‐based analysis of ERα‐mediated effects in bone‐forming cells in mice, in which the systemic ERα‐mediated effects are intact. In female ERαΔOB/ΔOB mice, trabecular and cortical bone volumes were significantly reduced (31.5 and 11.4%, respectively) at 3.5 mo of age compared with control ERαfl/fl animals, and their response to ovariectomy was small compared with that of controls. In contrast with females, no differences could be detected in the bone phenotype of young males, whereas in 6‐mo‐old ERαΔOB/ΔOB males, trabecular bone volume (Tb.BV) was decreased (27.5%). The ERα inactivation‐related effects were compared with those of controls having a similar genetic background. Parental osteocalcin‐Cre mice did not show Cre‐related changes. Our results suggest that in female mice, Tb.BV and cortical bone volume are critically dependent on the ERα regulation of osteoblasts, whereas in male mice, osteoblastic ERα is not required for the regulation of bone formation during rapid skeletal growth, but it is involved in the maintenance of Tb.BV.—Määttä, J. A., Büki, K. G., Gu, G., Alanne, M. H., Vääräniemi, J., Liljenbäck, H., Poutanen, M., Härkönen, P., Väänänen, K. Inactivation of estrogen receptor α in bone‐forming cells induces bone loss in female mice. FASEB J. 27, 478–488 (2013). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.12-213587