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药物调节初级纤毛的形成会影响骨细胞的机械敏感性。

Pharmacological Regulation of Primary Cilium Formation Affects the Mechanosensitivity of Osteocytes.

机构信息

Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, No. 37 Xueyuan Road, Haidian District, Beijing, 100083, China.

Beijing Key Laboratory of Rehabilitation Technical Aids for Old-Age Disability, National Research Center for Rehabilitation Technical Aids, Beijing, 100176, China.

出版信息

Calcif Tissue Int. 2020 Dec;107(6):625-635. doi: 10.1007/s00223-020-00756-6. Epub 2020 Sep 17.

Abstract

Primary cilia are responsible for sensing mechanical loading in osteocytes. However, the underlying working mechanism of cilia remains elusive. An osteocyte model is necessary to reveal the role of cilia. Furthermore, the osteocyte model should be with upregulated or downregulated primary cilium expression. Herein, we used a pharmacological method to regulate the cilium formation of osteocytes. After screening, some pharmacological agents can regulate the cilium formation of osteocytes. We performed a CCK-8 assay to analyze the optimal working conditions of the drugs for MLO-Y4 cells. The agents include chloral hydrate (CH), Gd, Li, and rapamycin. The expression of cilia affects the cellular functions, including mechanosensitivity, of osteocytes. Results showed that CH downregulated the cilium formation and ciliogenesis of osteocytes. In addition, Gd, Li, and rapamycin upregulated the cilium expression of osteocytes. Moreover, the cilium expression positively correlated with the mechanosensitivity of osteocytes. This work reveals the role of primary cilia in the mechanosensing of osteocytes.

摘要

初级纤毛负责感知破骨细胞中的机械负荷。然而,纤毛的潜在工作机制仍难以捉摸。需要破骨细胞模型来揭示纤毛的作用。此外,破骨细胞模型应该具有上调或下调的初级纤毛表达。在此,我们使用药理学方法来调节破骨细胞纤毛的形成。经过筛选,一些药理学试剂可以调节破骨细胞纤毛的形成。我们进行 CCK-8 分析来研究药物对 MLO-Y4 细胞的最佳工作条件。这些试剂包括水合氯醛(CH)、钆、锂和雷帕霉素。纤毛的表达影响破骨细胞的细胞功能,包括机械敏感性。结果表明,CH 下调破骨细胞的纤毛形成和纤毛发生。此外,钆、锂和雷帕霉素上调破骨细胞的纤毛表达。此外,纤毛的表达与破骨细胞的机械敏感性呈正相关。这项工作揭示了初级纤毛在破骨细胞机械感应中的作用。

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