Institute for Biomechanics, ETH Zurich, Leopold-Ruzicka-Weg 4, 8093, Zürich, Switzerland.
Curr Osteoporos Rep. 2018 Aug;16(4):395-403. doi: 10.1007/s11914-018-0448-6.
Connecting organ-scale loads to cellular signals in their local in vivo environment is a current challenge in the field of bone (re)modelling. Understanding this critical missing link would greatly improve our ability to anticipate mechanotransduction during different modes of stimuli and the resultant cellular responses. This review characterises computational approaches that could enable coupling links across the multiple scales of bone.
Current approaches using strain and fluid shear stress concepts have begun to link organ-scale loads to cellular signals; however, these approaches fail to capture localised micro-structural heterogeneities. Furthermore, models that incorporate downstream communication from osteocytes to osteoclasts, bone-lining cells and osteoblasts, will help improve the understanding of (re)modelling activities. Incorporating this potentially key information in the local in vivo environment will aid in developing multiscale models of mechanotransduction that can predict or help describe resultant biological events related to bone (re)modelling. Progress towards multiscale determination of the cell mechanical environment from organ-scale loads remains elusive. Construction of organ-, tissue- and cell-scale computational models that include localised environmental variation, strain amplification and intercellular communication mechanisms will ultimately help couple the hierarchal levels of bone.
将器官尺度的负载与局部体内环境中的细胞信号联系起来,是骨(重建)重塑领域的一个当前挑战。理解这一关键缺失环节将极大地提高我们在不同刺激模式下预测机械转导以及由此产生的细胞反应的能力。本综述描述了可以实现跨越多个骨骼尺度的连接的计算方法。
目前使用应变和流体切应力概念的方法已经开始将器官尺度的负载与细胞信号联系起来;然而,这些方法无法捕捉到局部微观结构的异质性。此外,将骨细胞向破骨细胞、骨衬细胞和成骨细胞的下游通讯纳入模型,将有助于提高对(重建)活动的理解。在局部体内环境中纳入这些潜在的关键信息,将有助于开发机械转导的多尺度模型,从而可以预测或有助于描述与骨(重建)相关的生物学事件。从器官尺度的负载向多尺度确定细胞力学环境的进展仍不明确。构建包括局部环境变化、应变放大和细胞间通讯机制的器官、组织和细胞尺度计算模型,最终将有助于连接骨骼的层次结构。