Middleton Kevin, Kondiboyina Avinash, Borrett Michael, Cui Yi, Mei Xueting, You Lidan
Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Room 407, Toronto, Ontario, M5S 3G9, Canada.
Division of Engineering Science, University of Toronto, 40 Saint George Street, Room 2110, Toronto, Ontario, M5S 2E4, Canada.
J Orthop Res. 2018 Feb;36(2):663-671. doi: 10.1002/jor.23773. Epub 2017 Nov 22.
Fluid flow is an important regulator of cell function and metabolism in many tissues. Fluid shear stresses have been used to level the mechanical stimuli applied in vitro with what occurs in vivo. However, these experiments often lack dynamic similarity, which is necessary to ensure the validity of the model. For interstitial fluid flow, the major requirement for dynamic similarity is the Reynolds number (Re), the ratio of inertial to viscous forces, is the same between the system and model. To study the necessity of dynamic similarity for cell mechanotransduction studies, we investigated the response of osteocyte-like MLO-Y4 cells to different Re flows at the same level of fluid shear stress. Osteocytes were chosen for this study as flows applied in vitro and in vivo have Re that are orders of magnitude different. We hypothesize that osteocytes' response to fluid flow is Re dependent. We observed that cells exposed to lower and higher Re flows developed rounded and triangular morphologies, respectively. Lower Re flows also reduced apoptosis rates compared to higher Re flows. Furthermore, MLO-Y4 cells exposed to higher Re flows had stronger calcium responses compared to lower Re flows. However, by also controlling for flow rate, the lower Re flows induced a stronger calcium response; while degradation of components of the osteocyte glycocalyx reversed this effect. This work suggests that osteocytes are highly sensitive to differences in Re, independent of just shear stresses, supporting the need for improved in vitro flow platforms that better recapitulate the physiological environment. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:663-671, 2018.
在许多组织中，流体流动是细胞功能和代谢的重要调节因子。流体剪切应力已被用于使体外施加的机械刺激与体内发生的情况相匹配。然而，这些实验往往缺乏动态相似性，而动态相似性是确保模型有效性所必需的。对于组织液流动，动态相似性的主要要求是系统和模型之间的雷诺数（Re），即惯性力与粘性力之比相同。为了研究细胞机械转导研究中动态相似性的必要性，我们研究了骨细胞样MLO - Y4细胞在相同流体剪切应力水平下对不同Re流的反应。本研究选择骨细胞是因为体外和体内施加的流的Re相差几个数量级。我们假设骨细胞对流体流动的反应依赖于Re。我们观察到，暴露于较低和较高Re流的细胞分别呈现圆形和三角形形态。与较高Re流相比，较低Re流也降低了细胞凋亡率。此外，与较低Re流相比，暴露于较高Re流的MLO - Y4细胞具有更强的钙反应。然而，通过控制流速，较低Re流诱导出更强的钙反应；而骨细胞糖萼成分的降解则逆转了这种效应。这项工作表明，骨细胞对Re的差异高度敏感，不仅仅取决于剪切应力，这支持了需要改进体外流动平台以更好地模拟生理环境的观点。© 2017骨科研究协会。由Wiley Periodicals, Inc.出版。《矫形外科研究杂志》36:663 - 671, 2018年。
