title: The effect of estrogen on bone requires ERα in nonhematopoietic cells but is enhanced by ERα in hematopoietic cells.
abstract: The effects of estrogen on bone are mediated mainly via estrogen receptor (ER)α. ERα in osteoclasts (hematopoietic origin) is involved in the trabecular bone-sparing effects of estrogen, but conflicting data are reported on the role of ERα in osteoblast lineage cells (nonhematopoietic origin) for bone metabolism. Because Cre-mediated cell-specific gene inactivation used in previous studies might be confounded by nonspecific and/or incomplete cell-specific ERα deletion, we herein used an alternative approach to determine the relative importance of ERα in hematopoietic (HC) and nonhematopoietic cells (NHC) for bone mass. Chimeric mice with selective inactivation of ERα in HC or NHC were created by bone marrow transplantations of wild-type (WT) and ERα-knockout (ERα(-/-)) mice. Estradiol treatment increased both trabecular and cortical bone mass in ovariectomized WT/WT (defined as recipient/donor) and WT/ERα(-/-) mice but not in ERα(-/-)/WT or ERα(-/-)/ERα(-/-) mice. However, estradiol effects on both bone compartments were reduced (∼50%) in WT/ERα(-/-) mice compared with WT/WT mice. The effects of estradiol on fat mass and B lymphopoiesis required ERα specifically in NHC and HC, respectively. In conclusion, ERα in NHC is required for the effects of estrogen on both trabecular and cortical bone, but these effects are enhanced by ERα in HC.
authors.affiliation: Centre for Bone and Arthritis Research.
authors.forename: Petra
authors.initials: P
authors.lastname: Henning
authors.affiliation: Centre for Bone and Arthritis Research.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Centre for Bone and Arthritis Research.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Engdahl
authors.affiliation: Centre for Bone and Arthritis Research.
authors.forename: Helen
authors.initials: H
authors.lastname: Farman
authors.affiliation: Centre for Bone and Arthritis Research.
authors.forename: Sara H
authors.initials: SH
authors.lastname: Windahl
authors.affiliation: Centre for Bone and Arthritis Research, Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
authors.affiliation: Centre for Bone and Arthritis Research, marie.lagerquist@gu.se.
authors.forename: Marie K
authors.initials: MK
authors.lastname: Lagerquist
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D016026:Bone Marrow Transplantation; D001842:Bone and Bones / Q000187:drug effects*; D002678:Chimera; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000187:drug effects*; D010010:Osteoclasts / Q000187:drug effects*; D010052:Ovariectomy
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D004958:Estradiol
keywords: bone marrow transplantation; cortical bone; estrogen; estrogen receptor-α; trabecular bone