Follicle-stimulating hormone promotes RANK expression on human monocytes.

Follicle-stimulating hormone promotes RANK expression on human monocytes.
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DOI:
10.1016/j.cyto.2010.11.011
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发表时间:
2011-02
期刊:
影响因子:
3.8
通讯作者:
Sloan G
Sloan G
中科院分区:
医学3区
文献类型:
--
作者:
Cannon JG;Kraj B;Sloan G

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卵泡刺激素(FSH)的血清浓度升高与女性骨密度降低有关,这种情况始于绝经前几年和雌二醇水平下降。我们假设FSH促进骨髓细胞向骨吸收破骨细胞表型发展。通过分离9名健康成人的外周血单个核细胞,将其在生理范围内的三种不同浓度的FSH中孵育,然后通过流式细胞术测量CD14+细胞上NF-κB受体激活剂(RANK,一种破骨细胞的表面标记物)的表达。在没有FSH的情况下,3.3±0.5%的细胞表达高水平的受体(RANKhigh)。FSH浓度的增加引起了双相剂量反应,当FSH浓度达到50 mIU/ml时,RANKhigh细胞的增幅最大(1.5倍)(P = 0.02)。在培养上清中也测量了影响破骨细胞发育的细胞因子:巨噬细胞集落刺激因子(M-CSF)、骨保护素(OPG)和肿瘤坏死因子-α (tnf -α)的浓度不受FSH的显著影响,而rank -配体则未检测到。这项研究支持了这样一种观点,即围绝经期FSH循环浓度的升高可能通过促进破骨细胞前体细胞的发育而增加骨质流失的速度。
Elevated serum concentrations of follicle-stimulating hormone (FSH) are associated with diminished bone density in women, beginning years before menopause and the decline in estradiol. We hypothesized that FSH promotes development of myeloid cells toward the bone-resorbing osteoclast phenotype. This was tested by isolating peripheral blood mononuclear cells from nine healthy adults, incubating them in the presence of FSH at three different concentrations spanning the physiological range, and then measuring the expression of receptor activator for NF-κB (RANK, a surface marker for osteoclasts) on CD14+ cells by flow cytometry. In the absence of FSH, 3.3 ± 0.5% of the cells expressed high levels of the receptor (RANKhigh). Increasing concentrations of FSH caused a biphasic dose-response, with a maximal (1.5-fold) increase in RANKhigh cells achieved with 50 mIU/ml FSH (P = 0.02). Cytokines that influence development of osteoclasts were also measured in culture supernatants: Macrophage colony stimulating factor (M-CSF), osteoprotegerin (OPG) and tumor necrosis factor-α (TNFα) concentrations were not significantly influenced by FSH, whereas RANK-ligand was undetectable. This study supports the concept that the elevated circulating concentrations of FSH during perimenopause may contribute to the increased rate of bone loss by promoting the development of osteoclast precursor cells.
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