Mechanobiological responses by osteoblasts are governed by downstream Rho-ROCK signalling through actin cytoskeleton re-arrangements but whether these responses are influenced by estrogen deficiency during osteoporosis remains unknown. The objective of this study was to determine alterations in the mechanobiological responses of estrogen-deficient osteoblasts and investigate whether an inhibitor of the Rho-ROCK signalling can revert these changes. MC3T3-E1 cells were pre-treated with 10 nM 17-β estradiol for 7 days and further cultured with or without estradiol for next 2 days. These cells were treated with or without ROCK-II inhibitor, Y-27632, and oscillatory fluid flow (OFF, 1Pa, 0.5 Hz, 1 h) was applied. Here, we report that Prostaglandin E₂ release, Runt-related transcription factor 2 and Osteopontin gene expression were significantly enhanced in response to OFF in estrogen-deficient cells than in cells with estrogen (3.73 vs 1.63 pg/ng DNA; 13.5 vs 2.6 fold, 2.1 vs 0.4 fold respectively). Upon ROCK-II inhibition, these enhanced effects of estrogen deficiency were downregulated. OFF increased the fibril anisotropy in cells pre-treated with estrogen and this increase was suppressed upon ROCK-II inhibition. This study is the first to demonstrate altered mechanobiological responses by osteoblasts during early estrogen deficiency and that these responses to OFF can be suppressed upon ROCK inhibition.

成骨细胞的力学生物学反应受肌动蛋白细胞骨架重排的下游Rho-ROCK信号控制，但这些反应是否受骨质疏松症期间雌激素缺乏影响尚不清楚。这项研究的目的是确定雌激素缺乏的成骨细胞的力学生物学反应的变化，并研究Rho-ROCK信号的抑制剂是否可以逆转这些变化。将MC3T3-E1细胞用10 nM17-β雌二醇预处理7天，然后在有或没有雌二醇的情况下进一步培养2天。在有或没有ROCK-II抑制剂Y-27632的情况下处理这些细胞，并施加振荡流体流量（OFF，1Pa，0.5 Hz，1 h）。在这里，我们报告前列腺素E ₂释放，与矮子相关的转录因子2与雌激素细胞相比，在雌激素缺乏的细胞中，对OFF的应答和骨桥蛋白基因表达显着增强（分别为3.73 vs 1.63 pg / ng DNA； 13.5 vs 2.6倍，2.1 vs 0.4倍）。在ROCK-II抑制后，雌激素缺乏的这些增强作用被下调。OFF增加了用雌激素预处理的细胞中的原纤维各向异性，并且这种增加在ROCK-II抑制下被抑制。这项研究是第一个证明在早期雌激素缺乏期间成骨细胞改变了机械生物学反应的方法，这些对OFF的反应可以在ROCK抑制后得到抑制。