17Beta-estradiol antagonizes effects of 1alpha,25-dihydroxyvitamin D3 on interleukin-6 production and osteoclast-like cell formation in mouse bone marrow primary cultures.
In mouse bone marrow primary cultures, the formation of osteoclast-like, i.e. tartrate-resistant acid phosphatase (TRAP)- and calcitonin receptor-positive multinucleated cells (MNC), when induced by 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), can be suppressed by 17beta-estradiol (17beta-E2), whereas 17alpha-E2 is without any effect. 17beta-E2, above 10(-11) M, significantly reduced 1alpha,25(OH)2D3-mediated TRAP+ MNC formation in cultured bone marrow cells from both female and male mice. The estrogen at 10(-8) M suppressed the peak response to the vitamin D sterol by 50%. 17beta-E2 significantly suppressed basal and 1alpha,25(OH)2D3-stimulated cellular production of interleukin (IL)-6. IL-6 alone, although bone marrow cells in hormone-free culture produced appreciable amounts of the cytokine, did not induce any TRAP+ MNC. Therefore, the changes in IL-6 production induced by the hormones could not be the sole determinant for the extent of TRAP+ MNC formation. However, the stimulatory effect of 1alpha,25(OH)2D3 on osteoclastogenesis nevertheless can be significantly reduced by a neutralizing monoclonal anti-IL-6 antibody. In the presence of 10(-8) M 17beta-E2, the anti-IL-6 monoclonal antibody does not achieve any further suppression of 1alpha,25(OH)2D3-related osteoclast-like cell formation. Our data suggest that induction of osteoclastogenesis by 1alpha,25(OH)2D3 is partially dependent on IL-6 signaling and can be modulated by 17beta-E2 through interference with IL-6 receptor activation, in addition to inhibition of IL-6 production by marrow stromal cells.
Schiller
C
C
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Gruber
R
R
Redlich
K
K
Ho
G M
GM
Katzgraber
F
F
Willheim
M
M
Pietschmann
P
P
Peterlik
M
M
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D018003:Receptors, Calcitonin / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D007527:Isoenzymes; D018003:Receptors, Calcitonin; D004958:Estradiol; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol