梯度流体剪应力下破骨前体细胞迁移与胞内钙分布关联性研究
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1.北京理工大学 宇航学院;2.首都体育学院 体育人工智能研究院

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Study on the correlation between cell migration and intracellular calcium distribution of osteoclast precursors under gradient fluid shear stress
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1.Biomechanics Lab,Department of Mechanics,School of Aerospace Engineering,Beijing Institute of Technology;2.Institute of Artificial Intelligence in Sports,Capital University of Physical Education and Sports

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    目的 阐明局部力学微环境下破骨前体细胞迁移的机制,即明确局部梯度流体剪应力是否会造成胞内Ca2+浓度梯度的特异性分布,并最终决定细胞的迁移方向。方法 利用COMSOL软件对流动腔内的流体剪应力分布进行数值模拟。建立流体剪应力作用下破骨前体细胞RAW264.7胞内Ca2+染色方法,并对细胞施加梯度流体剪应力,然后定量分析胞内Ca2+浓度分布和动态变化以及细胞迁移参数。 结果 实验结果表明,破骨前体细胞更倾向于向低流体剪应力区域迁移,且振荡流会调节细胞内Ca2+沿细胞迁移方向分布,当阻断力敏感阳离子选择性通道、磷脂酶C、内质网钙信号通路和清除细胞外钙后,细胞向低流体剪应力方向的迁移速度显著降低,但是沿液体流动方向的迁移速度显著增强,同时细胞沿液体流动方向的Ca2+分布显著升高。结论 梯度流体剪应力作用下,破骨前体细胞可以感受到这种梯度效应,且胞内Ca2+沿迁移方向的特异性分布,最终导致破骨前体细胞向低流体剪应力区域迁移。该结果为最终阐明动态外力作用下骨组织重建的细胞和分子机制提供了较为重要的基础数据。

    Abstract:

    Objective To explore the mechanism of osteoclast precursors’ migration under local mechanical microenvironment, specifically to determine whether local gradient fluid shear stress causes a specific distribution of intracellular calcium ion concentration, which ultimately determines the direction of cell migration. Methods Numerical simulations were performed using COMSOL software. The method of staining intracellular calcium ion for RAW264.7 osteoclast precursors was established. After applying gradient fluid shear stress on the cells, the distribution of intracellular calcium ion concentration and cell migration parameters were analyzed. Results Osteoclast precursors tend to migrate towards regions with lower fluid shear stress, and oscillatory flow regulates the distribution of intracellular calcium ions along the direction of cell migration. After blocking phospholipase C (PLC), mechanosensitive cation-selective channels (MSCC), endoplasmic reticulum (ER), and removing extracellular calcium, the migration speed of cells towards the low fluid shear stress direction was significantly reduced, but the migration speed along the liquid flow direction was significantly enhanced. Meanwhile, the calcium ion distribution along the liquid flow direction was significantly increased. Conclusions Osteoclast precursors can sense the fluid shear stress gradient, resulting in a specific distribution of intracellular calcium ions along the direction of migration. This ultimately leads to the migration of osteoclast precursors towards regions with lower fluid shear stress. This study provides important basic data for ultimately elucidating the cellular and molecular mechanisms of bone tissue remodeling under dynamic external forces.

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  • 收稿日期:2024-05-21
  • 最后修改日期:2024-06-11
  • 录用日期:2024-06-12
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