Mechanobiology and Medical Device Research Group (MMDRG), Biomedical Engineering, National University of, Ireland, Galway, Ireland.
Centre for Research in Medical Devices (CÚRAM), National University of Ireland, Galway, Ireland.
Sci Rep. 2019 Mar 15;9(1):4654. doi: 10.1038/s41598-019-41095-3.
The integrin αβ has been shown to play an important role in osteocyte mechanotransduction. It has been reported that there are fewer β integrin-containing cells in osteoporotic bone cells. Osteocytes cultured in vitro under estrogen deficient conditions demonstrate altered mechanotransduction. However, it is unknown whether the altered mechanotransduction in estrogen deficient osteocytes is directly associated with defective αβ expression or signalling. The objective of this study is to investigate the role of estrogen deficiency for regulating MLO-Y4 cell morphology, αβ expression, focal adhesion formation and mechanotransduction by osteocytes. Here, we report that estrogen withdrawal leads to a smaller focal adhesion area and reduced αβ localisation at focal adhesion sites, resulting in an increased Rankl/Opg ratio and defective Cox-2 responses to oscillatory fluid flow. Interestingly, αβ antagonism had a similar effect on focal adhesion assembly, Rankl/Opg ratio, and Cox-2 responses to oscillatory fluid flow. Taken together, our results provide the first evidence for a relationship between estrogen withdrawal and defective αβ-mediated signalling. Specifically, this study implicates estrogen withdrawal as a putative mechanism responsible for altered αβ expression and resultant changes in downstream signalling in osteocytes during post-menopausal osteoporosis, which might provide an important, but previously unidentified, contribution to the bone loss cascade.
整合素 αβ 在骨细胞机械转导中起着重要作用。据报道，骨质疏松症患者的骨细胞中β 整合素含量较少。在雌激素缺乏的条件下培养的体外骨细胞表现出改变的机械转导。然而，尚不清楚雌激素缺乏的骨细胞中改变的机械转导是否与αβ表达或信号的缺陷直接相关。本研究的目的是研究雌激素缺乏对调节成骨细胞 MLO-Y4 细胞形态、αβ 表达、黏附斑形成和机械转导的作用。在这里，我们报告说，雌激素耗竭导致黏附斑面积减小和黏附斑处αβ定位减少，导致 Rankl/Opg 比值增加和 Cox-2 对振荡液流的反应受损。有趣的是，αβ拮抗作用对黏附斑组装、Rankl/Opg 比值和 Cox-2 对振荡液流的反应也有类似的影响。总之，我们的研究结果首次提供了雌激素耗竭与缺陷的αβ 介导信号之间存在关系的证据。具体来说，本研究表明，雌激素耗竭可能是绝经后骨质疏松症中骨细胞中αβ 表达改变和下游信号改变的潜在机制，这可能为骨丢失级联提供一个重要但以前未被识别的贡献。
