title: Effects of Deletion of ERα in Osteoblast-Lineage Cells on Bone Mass and Adaptation to Mechanical Loading Differ in Female and Male Mice.
abstract: Estrogen receptor alpha (ERα) has been implicated in bone's response to mechanical loading in both males and females. ERα in osteoblast lineage cells is important for determining bone mass, but results depend on animal sex and the cellular stage at which ERα is deleted. We demonstrated previously that when ERα is deleted from mature osteoblasts and osteocytes in mixed-background female mice, bone mass and strength are decreased. However, few studies exist examining the skeletal response to loading in bone cell-specific ERαKO mice. Therefore, we crossed ERα floxed (ERα(fl/fl)) and osteocalcin-Cre (OC-Cre) mice to generate animals lacking ERα in mature osteoblasts and osteocytes (pOC-ERαKO) and littermate controls (LC). At 10 weeks of age, the left tibia was loaded in vivo for 2 weeks. We analyzed bone mass through micro-CT, bone formation rate by dynamic histomorphometry, bone strength from mechanical testing, and osteoblast and osteoclast activity by serum chemistry and immunohistochemistry. ERα in mature osteoblasts differentially regulated bone mass in males and females. Compared with LC, female pOC-ERαKO mice had decreased cortical and cancellous bone mass, whereas male pOC-ERαKO mice had equal or greater bone mass than LC. Bone mass results correlated with decreased compressive strength in pOC-ERαKO female L(5) vertebrae and with increased maximum moment in pOC-ERαKO male femora. Female pOC-ERαKO mice responded more to mechanical loading, whereas the response of pOC-ERαKO male animals was similar to their littermate controls.
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.|Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Melville
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.|Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
authors.forename: Natalie H
authors.initials: NH
authors.lastname: Kelly
authors.affiliation: Department of Biological Sciences, Cornell University, Ithaca, NY, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Surita
authors.affiliation: Department of Biological Sciences, Cornell University, Ithaca, NY, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Buchalter
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Schimenti
authors.affiliation: College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.|Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Main
authors.affiliation: Research Division, Hospital for Special Surgery, New York, NY, USA.
authors.forename: F Patrick
authors.initials: FP
authors.lastname: Ross
authors.affiliation: Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.|Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.|Research Division, Hospital for Special Surgery, New York, NY, USA.
authors.forename: Marjolein C H
authors.initials: MC
authors.lastname: van der Meulen
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D047628:Estrogen Receptor alpha / Q000172:deficiency*; D005260:Female; D008159:Lumbar Vertebrae / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010011:Osteocytes / Q000378:metabolism; D012727:Sex Characteristics; D013977:Tibia / Q000378:metabolism* / Q000473:pathology
chemical_list: D047628:Estrogen Receptor alpha; D015675:Osteocalcin
keywords: GENETIC ANIMAL MODEL; OSTEOBLASTS; OSTEOPOROSIS; SEX STEROIDS