Mechanobiology and Medical Device Research Group (MMDRG), Biomechanics Research Centre (BMEC), Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Galway, Ireland.
Mechanobiology and Medical Device Research Group (MMDRG), Biomechanics Research Centre (BMEC), Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Galway, Ireland; Lehigh University, Bethlehem, PA, USA.
Exp Cell Res. 2021 Nov 1;408(1):112814. doi: 10.1016/j.yexcr.2021.112814. Epub 2021 Sep 4.
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 MC3T3-E1 cells were pre-treated with estrogen for 14 days, after which estrogen was withdrawn or inhibited with Fulvestrant up to 14 days.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.
最近的研究表明，雌激素缺乏的影响不仅局限于破骨细胞和骨吸收，还会改变骨基质组成，使成骨细胞对机械刺激的反应受损。在这项研究中，我们通过体外实验验证了雌激素耗竭是否会改变机械刺激成骨细胞的成骨分化和基质产生的假设。MC3T3-E1 细胞先用雌激素预处理 14 天，然后用氟维司群（fulvestrant）去除或抑制雌激素，持续 14 天。采用轨道摇床施加流体切应力（FSS）。在静态培养中雌激素耗竭时，成骨标志物（ALP）和基因表达（Runx2）分别在雌激素耗竭 2 天和 7 天后降低。此外，在静态条件下，雌激素受体的抑制作用可显著降低纤连蛋白表达（FN1），持续至 7 天。在雌激素耗竭和每日机械刺激下，Runx2 的表达变化更早（4 天），而在 14 天时，基质产生（Col1a1）的变化也被报道。我们提出，雌激素耗竭期间成骨细胞分化的变化和基质产生受损可能导致骨质量改变，并成为绝经后骨质疏松症骨脆性增加的一个促成因素。
