Hum. Reprod. Advance Access originally published online on February 3, 2006
Human Reproduction 2006 21(4):880-887; doi:10.1093/humrep/dei413
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Alterations in the phenotype and function of immune cells in ovariectomy-induced osteopenic mice
1 Research Unit, Hospital Clínico Universitario of Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain, 2 Research Unit, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain, 3 Department of Physiology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain, 4 Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain, 5 Department of Functional Biology and Physical Anthropology, Faculty of Biological Sciences, University of Valencia, 46100 Burjassot, Spain and 6 Department of Pediatrics, Obstetrics and Gynecology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
7 To whom correspondence should be addressed. E-mail: miguel.garcia{at}uv.es
BACKGROUND: Within the last few years, much evidence has been presented on the involvement of the immune system in certain types of bone loss, such as activated T cells in rheumatoid arthritis and in periodontitis. Estrogen deficiency induces bone loss; however, how this deficiency affects the immune system has not been sufficiently studied. METHODS: To evaluate the effects of estrogen withdrawal on the status and functionality of the immune system, mice were ovariectomized or sham-operated, and 5 weeks after surgery, when osteopenia had developed, several parameters were analysed in spleen and in bone marrow. We analysed bone turnover, cell phenotype by flow cytometry, cell function by cell proliferation assays, and the expression of several genes related to the process. RESULTS: Five weeks after ovariectomy, augmented osteoclastogenesis persisted in the bone marrow. In addition, the ovariectomized mice had more B-cells and CD3+ T-cells expressing the receptor activator of NF-
B ligand (CD3+/RANKL+). The ovariectomized mice had lower serum alkaline phosphatase activity, a normal amount of T cells, lower percentages of CD11b+ and CD51+ cells in the bone marrow, and a lower serum interferon-
level compared with sham-operated controls. CONCLUSIONS: The data suggest that, 5 weeks after ovariectomy, bone turnover remains imbalanced, with increased osteoclastogenesis and a decreased rate of bone formation. Moreover, there is an increase in B-cell formation, with normal and decreased percentages of T cells and myelomonocytic cells (CD11b+), respectively, in the bone marrow. Decreased serum interferon- levels could be involved in the increased osteoclastogenesis found in the present work.
Key words: bone metabolism/estrogen deficiency/immune system/mouse/ovariectomy