title: Estrogen deficiency increases osteoclastogenesis up-regulating T cells activity: a key mechanism in osteoporosis.
abstract: Compelling evidences suggest that increased production of osteoclastogenic cytokines by activated T cells plays a relevant role in the bone loss induced by estrogen deficiency in the mouse. However, little information is available on the role of T cells in post-menopausal bone loss in humans. To investigate this issue we have assessed the production of cytokines involved in osteoclastogenesis (RANKL, TNFalpha and OPG), in vitro osteoclast (OC) formation in pre and post-menopausal women, the latter with or without osteoporosis. We evaluated also OC precursors in peripheral blood and the ability of peripheral blood mononuclear cells to produce TNFalpha in both basal and stimulated condition by flow cytometry in these subjects. Our data demonstrate that estrogen deficiency enhances the production of the pro-osteoclastogenetic cytokines TNFalpha and RANKL and increases the number of circulating OC precursors. Furthermore, we show that T cells and monocytes from women with osteoporosis exhibit a higher production of TNFalpha than those from the other two groups. Our findings suggest that estrogen deficiency stimulates OC formation both by increasing the production of TNFalpha and RANKL and increasing the number of OC precursors. Women with post-menopausal osteoporosis have a higher T cell activity than healthy post-menopausal subjects; T cells thus contribute to the bone loss induced by estrogen deficiency in humans as they do in the mouse.
authors.affiliation: Department of Internal Medicine, University of Torino, Italy. Electronic address: patrizia.damelio@unito.it.
authors.forename: Patrizia
authors.initials: P
authors.lastname: D'Amelio
authors.affiliation: Department of Internal Medicine, University of Torino, Italy.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Grimaldi
authors.affiliation: Department of Internal Medicine, University of Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Di Bella
authors.affiliation: Department of Internal Medicine, University of Torino, Italy.
authors.forename: Stefano Z M
authors.initials: SZM
authors.lastname: Brianza
authors.affiliation: Department of Internal Medicine, University of Torino, Italy.
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Cristofaro
authors.affiliation: Department of Internal Medicine, University of Torino, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tamone
authors.affiliation: Center for Experimental Research and Medical Studies (CERMS), Ospedale San Giovanni Battista, Torino, Italy; Department of Genetics, Biology and Biochemistry, University of Torino, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Giribaldi
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Torino, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ulliers
authors.affiliation: Center for Experimental Research and Medical Studies (CERMS), Ospedale San Giovanni Battista, Torino, Italy; Department of Genetics, Biology and Biochemistry, University of Torino, Italy.
authors.forename: Gian P
authors.initials: GP
authors.lastname: Pescarmona
authors.affiliation: Department of Internal Medicine, University of Torino, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Isaia
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D010010:Osteoclasts / Q000473:pathology*; D010024:Osteoporosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D017698:Postmenopause; D053245:RANK Ligand / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D004967:Estrogens; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha