A comparison of strain and fluid shear stress in stimulating bone cell responses - a computational and experimental study

A comparison of strain and fluid shear stress in stimulating bone cell responses - a computational and experimental study
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DOI:
10.1096/fj.04-2210fje
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发表时间:
2004-12-01
期刊:
影响因子:
4.8
通讯作者:
Prendergast, PJ
Prendergast, PJ
中科院分区:
生物学2区
文献类型:
--
作者:
McGarry, JG;Klein-Nulend, J;Prendergast, PJ

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骨骼响应机械负荷而不断重塑。然而,骨细胞对其不断变化的机械环境(即承载基质中的应变或通过微管网络的流体流动)做出反应的潜在机制尚不清楚。体外已证实骨细胞对基质应变和流体剪切应力处理的反应不同。揭示这些差异的力学基础对我们理解细胞力转导和骨重塑提出了重大挑战。为了研究这个问题,我们开发了贴壁细胞的生物力学模型,以检验骨细胞对 0.6 Pa 流体剪切应力和 1,000 muepsilon 基质应变刺激的不同反应的假设,因为引起的细胞变形的定性和定量差异。流体剪切应力加载条件导致细胞顶面的最大位移类似于细胞-基底界面处应变引起的位移的八倍,并且还导致细胞所有部分承受更高的应力。值得注意的是,这表明流体剪切应力和应变在细胞水平上的变形效果是不同的,这可能为解释几项研究中报道的骨细胞对两种刺激的反应差异提供基础。尽管我们对贴壁细胞的形态和复杂物理环境进行建模的方法肯定被简化了,但我们的结果确实显示了流体流动和应变作为机械刺激的独立作用,并强调了骨生理学中细胞水平变形的重要性。
Bone undergoes continuous remodeling in response to mechanical loading. However, the underlying mechanisms by which bone cells respond to their changing mechanical environment, that is, strain in the load-bearing matrix or fluid flow through the canalicular network, are not well understood. It has been established in vitro that bone cells respond differently to substrate strain and fluid shear stress treatments. Uncovering the mechanical basis of these differences represents a significant challenge to our understanding of cellular mechanotransduction and bone remodeling. To investigate this problem, we developed a biomechanical model of an adherent cell, to test the hypothesis that bone cells respond differently to 0.6 Pa fluid shear stress and 1,000 muepsilon substrate strain stimulation because of qualitative and quantitative differences in the cellular deformation caused. Fluid shear stress loading conditions resulted in maximum displacements at the apical surface of the cell similar to8 times higher than those due to strain at the cell-substrate interface and also caused higher stressing of all parts of the cell. Significantly, this shows that the deforming effects of fluid shear stress and strain on a cellular level are qualitatively different, which may provide a basis for explaining differences in bone cell responses to both stimuli as reported in several studies. Although our approach to modeling the morphology and complex physical environment of an adherent cell is certainly simplified, our results do show independent roles for fluid flow and strain as mechanical stimuli and highlight the importance of deformation on a cellular level in bone physiology.