Schiller C, Gruber R, Redlich K, Ho G M, Katzgraber F, Willheim M, Pietschmann P, Peterlik M
Department of General and Experimental Pathology, University of Vienna Medical School, Austria.
Endocrinology. 1997 Nov;138(11):4567-71. doi: 10.1210/endo.138.11.5523.
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.
在小鼠骨髓原代培养中，1α,25 - 二羟基维生素D3（1α,25(OH)2D3）诱导产生的抗酒石酸酸性磷酸酶（TRAP）和降钙素受体阳性的多核细胞（MNC），即破骨细胞样细胞的形成，可被17β - 雌二醇（17β - E2）抑制，而17α - E2则无任何作用。浓度高于10(-11) M的17β - E2能显著减少来自雌性和雄性小鼠的培养骨髓细胞中1α,25(OH)2D3介导的TRAP + MNC形成。10(-8) M的雌激素使对维生素D甾醇的峰值反应抑制了50%。17β - E2显著抑制基础状态以及1α,25(OH)2D3刺激的白细胞介素（IL）-6的细胞产生。单独的IL - 6，尽管无激素培养的骨髓细胞能产生相当数量的这种细胞因子，但并未诱导任何TRAP + MNC。因此，激素诱导的IL - 6产生变化并非TRAP + MNC形成程度的唯一决定因素。然而，1α,25(OH)2D3对破骨细胞生成的刺激作用仍可被一种中和性抗IL - 6单克隆抗体显著降低。在存在10(-8) M 17β - E2的情况下，抗IL - 6单克隆抗体并不能进一步抑制1α,25(OH)2D3相关的破骨细胞样细胞形成。我们的数据表明，1α,25(OH)2D3诱导破骨细胞生成部分依赖于IL - 6信号传导，并且除了抑制骨髓基质细胞产生IL - 6外，17β - E2还可通过干扰IL - 6受体激活来对其进行调节。
