Microscale fluid flow analysis in a human osteocyte canaliculus using a realistic high-resolution image-based three-dimensional model
Microscale fluid flow analysis in a human osteocyte canaliculus using a realistic high-resolution image-based three-dimensional model
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DOI：
10.1039/c2ib20092a
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发表时间：
2012-01-01
影响因子：
2.5
通讯作者：
Klein-Nulend, Jenneke
中科院分区：
文献类型：
--
作者：
Kamioka, Hiroshi;Kameo, Yoshitaka;Klein-Nulend, Jenneke
骨细胞在骨骼质量的调节中起着关键作用。骨细胞的过程被认为是感知间质液的流动，这些间质液是由施加在骨上的机械刺激驱动通过骨细胞小管的，但是这种流动如何引起细胞反应实际上是未知的。现代理论模型假设骨细胞小管包含放大流体流动衍生的机械信号的超微结构特征。不幸的是，钙化的骨基质大大阻碍了骨细胞在其小管内过程的研究。使用世界上为数不多的超高压电子显微镜（UHVEM），我们应用UHVEM断层扫描在2兆电子伏重建独特的三维图像骨细胞小管在1 μ m的部分人骨。建立了具有真实感的单根泪小管三维图像模型，分析了泪小管内牛顿流体流动的流体动力学特性。我们通过小管创建了虚拟的2.2 nm厚的切片，发现传统的TEM技术产生了一种错误的印象，即骨细胞突起直接附着在小管壁上。小管壁具有高度不规则的表面，并含有大小和形状与胶原纤维相似的突出轴对称结构。我们还发现，小管壁的微观表面粗糙度强烈影响流体流动剖面，从而出现高度不均匀的流动模式。这些不均匀的流动模式可能会导致骨细胞过程中的细胞骨架元件变形，从而放大机械信号。基于这些观察，新的和现实的模型可以开发，这将显着提高我们的理解的过程中的骨mechanotransduction。
Osteocytes play a pivotal role in the regulation of skeletal mass. Osteocyte processes are thought to sense the flow of interstitial fluid that is driven through the osteocyte canaliculi by mechanical stimuli placed upon bone, but how this flow elicits a cellular response is virtually unknown. Modern theoretical models assume that osteocyte canaliculi contain ultrastructural features that amplify the fluid flow-derived mechanical signal. Unfortunately the calcified bone matrix has considerably hampered studies on the osteocyte process within its canaliculus. Using one of the few ultra high voltage electron microscopes (UHVEM) available worldwide, we applied UHVEM tomography at 2 MeV to reconstruct unique three-dimensional images of osteocyte canaliculi in 1 mu m sections of human bone. A realistic three-dimensional image-based model of a single canaliculus was constructed, and the fluid dynamics of a Newtonian fluid flow within the canaliculus was analyzed. We created virtual 2.2 nm thick sections through a canaliculus and found that traditional TEM techniques create a false impression that osteocyte processes are directly attached to the canalicular wall. The canalicular wall had a highly irregular surface and contained protruding axisymmetric structures similar in size and shape to collagen fibrils. We also found that the microscopic surface roughness of the canalicular wall strongly influenced the fluid flow profiles, whereby highly inhomogeneous flow patterns emerged. These inhomogeneous flow patterns may induce deformation of cytoskeletal elements in the osteocyte process, thereby amplifying mechanical signals. Based on these observations, new and realistic models can be developed that will significantly enhance our understanding of the process of mechanotransduction in bone.