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首页> 外文期刊>Scientific reports. >Simulated microgravity inhibits L-type calcium channel currents partially by the up-regulation of miR-103 in MC3T3-E1 osteoblasts
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Simulated microgravity inhibits L-type calcium channel currents partially by the up-regulation of miR-103 in MC3T3-E1 osteoblasts

机译：模拟微重力通过上调MC3T3-E1成骨细胞中miR-103的表达部分抑制L型钙通道电流

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L-type voltage-sensitive calcium channels (LTCCs), particularly Cav1.2 LTCCs, play fundamental roles in cellular responses to mechanical stimuli in osteoblasts. Numerous studies have shown that mechanical loading promotes bone formation, whereas the removal of this stimulus under microgravity conditions results in a reduction in bone mass. However, whether microgravity exerts an influence on LTCCs in osteoblasts and whether this influence is a possible mechanism underlying the observed bone loss remain unclear. In the present study, we demonstrated that simulated microgravity substantially inhibited LTCC currents and suppressed Cav1.2 at the protein level in MC3T3-E1 osteoblast-like cells. In addition, reduced Cav1.2 protein levels decreased LTCC currents in MC3T3-E1 cells. Moreover, simulated microgravity increased miR-103 expression. Cav1.2 expression and LTCC current densities both significantly increased in cells that were transfected with a miR-103 inhibitor under mechanical unloading conditions. These results suggest that simulated microgravity substantially inhibits LTCC currents in osteoblasts by suppressing Cav1.2 expression. Furthermore, the down-regulation of Cav1.2 expression and the inhibition of LTCCs caused by mechanical unloading in osteoblasts are partially due to miR-103 up-regulation. Our study provides a novel mechanism for microgravity-induced detrimental effects on osteoblasts, offering a new avenue to further investigate the bone loss induced by microgravity.
机译：L型电压敏感钙通道（LTCC），尤其是Cav1.2 LTCC，在成骨细胞对机械刺激的细胞反应中起着基本作用。大量研究表明，机械负荷会促进骨形成，而在微重力条件下去除这种刺激会导致骨量减少。但是，微重力是否会对成骨细胞中的LTCC产生影响，以及这种影响是否是观察到的骨丢失的潜在机制尚不清楚。在本研究中，我们证明了模拟微重力在MC3T3-E1成骨细胞样细胞的蛋白质水平上基本上抑制了LTCC电流并抑制了Cav1.2。此外，降低的Cav1.2蛋白水平可降低MC3T3-E1细胞中的LTCC电流。此外，模拟微重力增加了miR-103的表达。在机械卸载条件下，用miR-103抑制剂转染的细胞中Cav1.2表达和LTCC电流密度均显着增加。这些结果表明，模拟的微重力通过抑制Cav1.2表达而实质上抑制了成骨细胞中的LTCC电流。此外，成骨细胞中机械卸载引起的Cav1.2表达的下调和LTCC的抑制部分归因于miR-103的上调。我们的研究为微重力对成骨细胞的有害作用提供了新的机制，为进一步研究微重力引起的骨质流失提供了新途径。

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