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Estrogen depletion alters osteogenic differentiation and matrix production by osteoblasts in vitro
Experimental Cell Research ( IF 3.3 ) Pub Date : 2021-09-04 , DOI: 10.1016/j.yexcr.2021.112814
J Schiavi 1 , D M Fodera 2 , M A Brennan 1 , L M McNamara 1
Affiliation  

Recent studies have revealed that the effects of estrogen deficiency are not restricted to osteoclasts and bone resorption, but that bone matrix composition is altered and osteoblasts exhibit an impaired response to mechanical stimulation. In this study, we test the hypothesis that estrogen depletion alters osteogenic differentiation and matrix production by mechanically stimulated osteoblasts in vitro. MC3T3-E1 cells were pre-treated with estrogen for 14 days, after which estrogen was withdrawn or inhibited with Fulvestrant up to 14 days. Fluid shear stress (FSS) was applied using an orbital shaker. Under estrogen depletion in static culture, osteogenic marker (ALP) and gene expression (Runx2) were decreased at 2 and after 7 days of estrogen depletion, respectively. In addition, up to 7 day the inhibition of the estrogen receptor significantly decreased fibronectin expression (FN1) under static conditions. Under estrogen depletion and daily mechanical stimulation, changes in expression of Runx2 occurred earlier (4 days) and by 14 days, changes in matrix production (Col1a1) were reported. We propose that changes in osteoblast differentiation and impaired matrix production during estrogen depletion may contribute to the altered quality of the bone and act as a contributing factor to increased bone fragility in postmenopausal osteoporosis.



中文翻译:

雌激素耗竭改变体外成骨细胞的成骨分化和基质产生

最近的研究表明,雌激素缺乏的影响不仅限于破骨细胞和骨吸收,而且骨基质成分发生改变,成骨细胞对机械刺激的反应受损。在这项研究中,我们测试了以下假设:雌激素耗竭会通过体外机械刺激的成骨细胞改变成骨分化和基质产生。MC3T3-E1 细胞用雌激素预处理 14 天,然后停用雌激素或用氟维司群抑制长达 14 天。使用定轨振荡器施加流体剪切应力 (FSS)。在静态培养中雌激素耗竭下,成骨标志物 (ALP) 和基因表达 ( Runx2) 分别在雌激素耗尽 2 天和 7 天后下降。此外,在静态条件下,长达 7 天的雌激素受体抑制显着降低了纤连蛋白表达 ( FN1 )。在雌激素耗竭和每日机械刺激下,Runx2表达的变化发生得更早(4 天),到 14 天时,报告了基质产生 ( Col1a1 ) 的变化。我们提出,在雌激素耗竭期间成骨细胞分化的变化和基质生成受损可能会导致骨质量的改变,并且是导致绝经后骨质疏松症骨脆性增加的一个促成因素。

更新日期:2021-09-04
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