Alterations in the phenotype and function of immune cells in ovariectomy-induced osteopenic mice.
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-kappaB 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-gamma 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-gamma levels could be involved in the increased osteoclastogenesis found in the present work.
García-Pérez
M A
MA
Research Unit, Hospital Clínico Universitario of Valencia, Av. Blasco Ibáñez 17, 46010 Valencia, Spain. miguel.garcia@uv.es
Noguera
I
I
Hermenegildo
C
C
Martínez-Romero
A
A
Tarín
J J
JJ
Cano
A
A
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000097:blood; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D010052:Ovariectomy; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D014599:Uterus / Q000473:pathology
D004967:Estrogens; D016328:NF-kappa B; D007371:Interferon-gamma; D000469:Alkaline Phosphatase