Osteocytes form over 90% of the bone cells and are postulated to be mechanosensors responsible for regulating the function of osteoclasts and osteoblasts in bone modeling and remodeling. Physical activity results in mechanical loading on the bones. Osteocytes are thought to be the main mechanosensory cells in bone. Upon load osteocytes secrete key factors initiating downstream signaling pathways that regulate skeletal metabolism including the Wnt/β-catenin signaling pathway. Osteocytes have dendritic structures and are housed in the lacunae and canaliculi within the bone matrix. Mechanical loading is known to have two primary effects, namely a mechanical strain (membrane disruption by stretching) on the lacunae/cells, and fluid flow, in the form of fluid flow shear stress (FFSS), in the space between the cell membranes and the lacuna-canalicular walls. In response, osteocytes get activated via a process called mechanotransduction in which mechanical signals are transduced to biological responses. The study of mechanotransduction is a complex subject involving principles of engineering mechanics as well as biological signaling pathway studies. Several length scales are involved as the mechanical loading on macro sized bones are converted to strain and FFSS responses at the micro-cellular level. Experimental measurements of strain and FFSS at the cellular level are very difficult and correlating them to specific biological activity makes this a very challenging task. One of the methods commonly adopted is a multi-scale approach that combines biological and mechanical experimentation with in silico numerical modeling of the engineering aspects of the problem. Finite element analysis along with fluid-structure interaction methodologies are used to compute the mechanical strain and FFSS. These types of analyses often involve a multi-length scale approach where models of both the macro bone structure and micro structure at the cellular length scale are used. Imaging modalities play a crucial role in the development of the models and present their own challenges. This paper reviews the efforts of various research groups in addressing this problem and presents the work in our research group. A clear understanding of how mechanical stimuli affect the lacunae and perilacunar tissue strains and shear stresses on the cellular membranes may ultimately lead to a better understanding of the process of osteocyte activation.

中文翻译：

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骨细胞腔隙系统机械应变和流体流动的多尺度有限元建模

骨细胞形成超过 90% 的骨细胞，并被假定为负责调节破骨细胞和成骨细胞在骨骼建模和重塑中的功能的机械传感器。体力活动会导致骨骼承受机械负荷。骨细胞被认为是骨骼中的主要机械感觉细胞。加载后，骨细胞分泌关键因子，启动下游信号通路，调节骨骼代谢，包括 Wnt/β-catenin 信号通路。骨细胞具有树突状结构并位于骨基质内的腔隙和小管中。已知机械载荷有两个主要影响，即对腔隙/细胞的机械应变（膜因拉伸而破裂）和流体流动，以流体流动剪切应力 (FFSS) 的形式，在细胞膜和腔隙小管壁之间的空间中。作为回应，骨细胞通过称为机械转导的过程被激活，在该过程中机械信号被转导为生物反应。机械转导研究是一门复杂的学科，涉及工程力学原理和生物信号通路研究。当宏观尺寸的骨骼上的机械载荷被转换为微细胞水平的应变和 FFSS 响应时，涉及几个长度尺度。在细胞水平上对应变和 FFSS 进行实验测量非常困难，并且将它们与特定的生物活性相关联使得这是一项非常具有挑战性的任务。通常采用的方法之一是多尺度方法，它将生物和机械实验与问题工程方面的计算机数值建模相结合。有限元分析以及流固耦合方法用于计算机械应变和 FFSS。这些类型的分析通常涉及多长度尺度方法，其中使用细胞长度尺度的宏观骨骼结构和微观结构模型。成像模式在模型的开发中起着至关重要的作用，并提出了自己的挑战。本文回顾了各个研究小组在解决这个问题方面所做的努力，并介绍了我们研究小组的工作。