title: Inhibition of bone resorption by 17beta-estradiol in human bone marrow cultures.
abstract: Estrogen deficiency puts individuals at risk of developing osteoporosis because it causes increased bone resorption. However, the mechanism by which this occurs is not known. We have shown, using a recently described two-phase human bone marrow culture system, that estradiol (17beta-E2) added to phase I results in inhibition of bone resorption by reducing the number of osteoclasts (identified as vitronectin receptor and/or calcitonin receptor-positive cells) formed in the cultures. The addition of 17beta-E2 in phase II was without effect, indicating that it does not interfere with the bone resorptive process. 17Beta-E2 down-regulated mRNA expression and protein synthesis of the membrane form of macrophage colony-stimulating factor (M-CSF). 17Beta-E2 did not the alter the expression of the 4.0 kb M-CSF transcript. However, it increased protein synthesis of the proteoglycan form of M-CSF, but not the 85 kDa soluble form in the same cultures. Finally, addition of M-CSF to the cultures reversed the 17beta-E2-induced inhibitory effect. These observations suggest that regulation of the synthesis of membrane-bound M-CSF plays a role in 17beta-E2-induced inhibition of bone resorption.
authors.affiliation: Department of Histopathology, Imperial College School of Medicine at St. Mary's, London, United Kingdom.
authors.forename: U
authors.initials: U
authors.lastname: Sarma
authors.forename: M
authors.initials: M
authors.lastname: Edwards
authors.forename: K
authors.initials: K
authors.lastname: Motoyoshi
authors.forename: A M
authors.initials: AM
authors.lastname: Flanagan
mesh_terms: D000199:Actins / Q000235:genetics; D000911:Antibodies, Monoclonal; D001854:Bone Marrow Cells / Q000166:cytology*; D001862:Bone Resorption; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D016173:Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry / Q000166:cytology; D010010:Osteoclasts / Q000737:chemistry / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D019030:Receptors, Vitronectin / Q000032:analysis
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D019030:Receptors, Vitronectin; D004958:Estradiol; D016173:Macrophage Colony-Stimulating Factor