Osteocyte lacunar strain determination using multiscale finite element analysis
Osteocyte lacunar strain determination using multiscale finite element analysis
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DOI：
10.1016/j.bonr.2020.100277
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发表时间：
2020-06-01
期刊：
影响因子：
2.5
通讯作者：
Ganesh, Thiagarajan
中科院分区：
文献类型：
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作者：
Kola, Sravan K.;Begonia, Mark T.;Ganesh, Thiagarajan
骨细胞被认为是骨中主要的机械感觉细胞，通过调节破骨细胞和成骨细胞来控制负荷引起的骨吸收和骨形成的变化。骨细胞在受到机械力后启动细胞内反应，包括激活Wnt/β-catenin信号通路。作为对变化的机械载荷(应变)的响应，骨细胞向骨表面的细胞发出信号。然而，这种骨细胞激活的过程似乎是异质性的，因为它发生在骨细胞亚群中，甚至在基于传统有限元建模方法确定的类似全球应变大小的区域内也是如此。一些研究已经使用有限元(FE)模型研究了骨细胞陷窝的应变响应，但许多研究都受到使用理想化几何(例如椭球体)和对单个骨细胞的分析的限制。其他小组的有限元模型包含了更多细节，如小管，但所有的模型都是由单个骨细胞组成的模型。我们假设骨内骨细胞陷窝的大小和取向的变化将导致应变场中的微观异质性，这可以更好地解释观察到的骨细胞在加载后的激活模式。在我们的微尺度和纳米尺度模型中，骨细胞具有理想的椭圆形，其中一些是基于共聚焦扫描的。然而，在这个初步研究中，所有的FE模型都是由多个骨细胞组成的。3D共聚焦扫描模型中的骨细胞数量从5到17个不等。在这项研究中，首先使用多尺度计算方法建立了微尺度水平的骨细胞有限元模型，基于两个参数：1)腔隙方向和2)腔隙大小，来检验理论腔隙和腔隙周围的应变响应。通过稳步增加楔周模数(5、10、15和20 GPA)进行参数分析。其次，使用已知的骨细胞尺寸建立纳米尺度的有限元模型，以确定预测的楔周基质、流体空间和细胞体区域的应变。最后，使用来自小鼠股骨的共焦图像堆叠来创建3-D腔隙模型，以确定由真实几何形状表示的腔隙中的理论应变。总的来说，随着楔周模数的增加，腔隙应变在细胞体中减少了14%，在液体间隙中减少了15%，在楔周间隙中减少了25%，表明了应力屏蔽作用。与垂直于加载轴排列的骨细胞相比，沿加载轴排列的骨细胞的骨陷窝应变较低。腔隙大小的增加也会导致腔隙菌株的增加。这些有限元模型的发现表明，在活体施加机械载荷后，骨细胞应变响应的不同初始模式可能与骨的取向和骨陷窝的大小有关。更好地了解机械刺激是如何直接影响骨陷窝和牙槽周围组织应变的，最终可能会更好地理解骨细胞在机械负荷下的激活过程。
Osteocytes are thought to be the primary mechanosensory cells within bone, regulating both osteoclasts and osteoblasts to control load induced changes in bone resorption and formation. Osteocytes initiate intracellular responses including activating the Wnt/beta-catenin signaling pathway after experiencing mechanical forces. In response to changing mechanical loads (strain) the osteocytes signal to cells on the bone surface. However, this process of osteocyte activation appears heterogeneous since it occurs in sub-populations of osteocytes, even within regions predicted to be experiencing similar global strain magnitudes determined based on traditional finite element modeling approaches. Several studies have investigated the strain responses of osteocyte lacunae using finite element (FE) models, but many were limited by the use of idealized geometries (e.g., ellipsoids) and analysis of a single osteocyte. Finite element models by other groups included more details, such as canaliculi, but all were done on models consisting of a single osteocyte. We hypothesized that variation in size and orientation of the osteocyte lacunae within bone would give rise to micro heterogeneity in the strain fields that could better explain the observed patterns of osteocyte activation following load. The osteocytes in our microscale and nanoscale models have an idealized oval shape and some are based on confocal scans. However, all the FE models in this preliminary study consist of multiple osteocytes. The number of osteocytes in the 3D confocal scan models ranged from five to seventeen. In this study, a multi-scale computational approach was used to first create an osteocyte FE model at the microscale level to examine both the theoretical lacunar and perilacunar strain responses based on two parameters: 1) lacunar orientation and 2) lacunar size. A parametric analysis was performed by steadily increasing the perilacunar modulus (5, 10, 15, and 20 GPa). Secondly, a nanoscale FE model was built using known osteocyte dimensions to determine the predicted strains in the perilacunar matrix, fluid space, and cell body regions. Finally, 3-D lacunar models were created using confocal image stacks from mouse femurs to determine the theoretical strain in the lacunae represented by realistic geometries. Overall, lacunar strains decreased by 14% in the cell body, 15% in the fluid space region and 25% in the perilacunar space as the perilacunar modulus increased, indicating a stress shielding effect. Lacunar strains were lower for the osteocytes aligned along the loading axis compared to those aligned perpendicular to axis. Increases in lacuna size also led to increased lacunar strains. These finite element model findings suggest that orientation and lacunar size may contribute to the heterogeneous initial pattern of osteocyte strain response observed in bone following in vivo applied mechanical loads. A better understanding of how mechanical stimuli directly affect the lacunae and perilacunar tissue strains may ultimately lead to a better understanding of the process of osteocyte activation in response to mechanical loading.