This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schiller, C. Articles by Peterlik, M. Search for Related Content PubMed PubMed Citation Articles by Schiller, C. Articles by Peterlik, M.

17ß-Estradiol Antagonizes Effects of 1,25-Dihydroxyvitamin D₃ on Interleukin-6 Production and Osteoclast-Like Cell Formation in Mouse Bone Marrow Primary Cultures¹

Department of General and Experimental Pathology, University of Vienna Medical School, A-1090 Vienna, Austria

Address all correspondence and requests for reprints to: Dr. Meinrad Peterlik, Department of General and Experimental Pathology, Neubau AKH, Waehringer Guertel 18–20, A-1090 Vienna, Austria.

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 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), can be suppressed by 17ß-estradiol (17ß-E₂), whereas 17-E₂ is without any effect. 17ß-E₂, above 10^-11 M, significantly reduced 1,25(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%. 17ß-E₂ significantly suppressed basal and 1,25(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 1,25(OH)₂D₃ on osteoclastogenesis nevertheless can be significantly reduced by a neutralizing monoclonal anti-IL-6 antibody. In the presence of 10^-8 M 17ß-E₂, the anti-IL-6 monoclonal antibody does not achieve any further suppression of 1,25(OH)₂D₃-related osteoclast-like cell formation. Our data suggest that induction of osteoclastogenesis by 1,25(OH)₂D₃ is partially dependent on IL-6 signaling and can be modulated by 17ß-E₂ through interference with IL-6 receptor activation, in addition to inhibition of IL-6 production by marrow stromal cells.

This article has been cited by other articles:

				R. H. Straub The Complex Role of Estrogens in Inflammation Endocr. Rev., August 1, 2007; 28(5): 521 - 574. [Abstract] [Full Text] [PDF]

				K. E. Broderick, T. Zhang, H. Rangaswami, Y. Zeng, X. Zhao, G. R. Boss, and R. B. Pilz Guanosine 3',5'-Cyclic Monophosphate (cGMP)/cGMP-Dependent Protein Kinase Induce Interleukin-6 Transcription in Osteoblasts Mol. Endocrinol., May 1, 2007; 21(5): 1148 - 1162. [Abstract] [Full Text] [PDF]

				X.-H. Liu, A. Kirschenbaum, S. Yao, and A. C. Levine Cross-Talk between the Interleukin-6 and Prostaglandin E2 Signaling Systems Results in Enhancement of Osteoclastogenesis through Effects on the Osteoprotegerin/Receptor Activator of Nuclear Factor-{kappa}B (RANK) Ligand/RANK System Endocrinology, April 1, 2005; 146(4): 1991 - 1998. [Abstract] [Full Text] [PDF]

				S M Aronica, A Dozier, P Fanti, and M Nazareth Altered bone marrow cell sensitivity in the lupus-prone NZB/W mouse: regulation of CFU-GM colony formation by estrogen, tamoxifen and thrombopoietin Lupus, May 1, 2000; 9(4): 271 - 277. [Abstract] [PDF]

				M. Willheim, R. Thien, K. Schrattbauer, E. Bajna, M. Holub, R. Gruber, K. Baier, P. Pietschmann, W. Reinisch, O. Scheiner, et al. Regulatory Effects of 1{alpha},25-Dihydroxyvitamin D3 on the Cytokine Production of Human Peripheral Blood Lymphocytes J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3739 - 3744. [Abstract] [Full Text] [PDF]