Simulated microgravity reduces intracellular-free calcium concentration by inhibiting calcium channels in primary mouse osteoblasts

模拟微重力通过抑制小鼠原代成骨细胞中的钙通道降低细胞内游离钙浓度

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作者:Zhongyang Sun, Ying Li, Hua Zhou, Min Cai, Jing Liu, Shanshan Gao, Junsheng Yang, Liangcheng Tong, Jianling Wang, Sheng Zhou, Zebing Hu, Yixuan Wang, Ke Wang, Lijun Zhang, Han Wang, Lianchang Zhang, Fei Shi, Xinsheng Cao, Shu Zhang, Yongzhang Ji, Jianning Zhao

Abstract

Calcium homeostasis in osteoblasts plays fundamental roles in the physiology and pathology of bone tissue. Various types of mechanical stimuli promote osteogenesis and increase bone formation elicit increases in intracellular-free calcium concentration in osteoblasts. However, whether microgravity, a condition of mechanical unloading, exerts an influence on intracellular-free calcium concentration in osteoblasts or what mechanisms may underlie such an effect are unclear. Herein, we show that simulated microgravity reduces intracellular-free calcium concentration in primary mouse osteoblasts. In addition, simulated microgravity substantially suppresses the activities of L-type voltage-sensitive calcium channels, which selectively allow calcium to cross the plasma membrane from the extracellular space. Moreover, the functional expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors, which mediate the release of calcium from intracellular storage, decreased under simulated microgravity conditions. These results suggest that simulated microgravity substantially reduces intracellular-free calcium concentration through inhibition of calcium channels in primary mouse osteoblasts. Our study may provide a novel mechanism for microgravity-induced detrimental effects in osteoblasts, offering a new avenue to further investigate bone loss induced by mechanical unloading.

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