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体内 microCT 时间 lapse 形态计量学揭示了骨(再)建模的解剖部位特异性差异,可作为检测早期病理事件的基线参数。

In vivo microCT-based time-lapse morphometry reveals anatomical site-specific differences in bone (re)modeling serving as baseline parameters to detect early pathological events.

机构信息

Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany.

Department of Biomaterials, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany; Research Centre, Shriners Hospital for Children-Canada, Montreal, Canada; Department of Pediatric Surgery, McGill University, Montreal, Canada.

出版信息

Bone. 2022 Aug;161:116432. doi: 10.1016/j.bone.2022.116432. Epub 2022 May 12.

DOI:10.1016/j.bone.2022.116432
PMID:35569733
Abstract

The bone structure is very dynamic and continuously adapts its geometry to external stimuli by modeling and remodeling the mineralized tissue. In vivo microCT-based time-lapse morphometry is a powerful tool to study the temporal and spatial dynamics of bone (re)modeling. Here an advancement in the methodology to detect and quantify site-specific differences in bone (re)modeling of 12-week-old BALB/c nude mice is presented. We describe our method of quantifying new bone surface interface readouts and how these are influenced by bone curvature. This method is then used to compare bone surface (re)modeling in mice across different anatomical regions to demonstrate variations in the rate of change and spatial gradients thereof. Significant differences in bone (re)modeling baseline parameters between the metaphyseal and epiphyseal, as well as cortical and trabecular bone of the distal femur and proximal tibia are shown. These results are validated using conventional static in vivo microCT analysis. Finally, the insights from these new baseline values of physiological bone (re)modeling were used to evaluate pathological bone (re)modeling in a pilot breast cancer bone metastasis model. The method shows the potential to be suitable to detect early pathological events and track their spatio-temporal development in both cortical and trabecular bone. This advancement in (re)modeling surface analysis and defined baseline parameters according to distinct anatomical regions will be valuable to others investigating various disease models with site-distinct local alterations in bone (re)modeling.

摘要

骨骼结构非常活跃,通过对矿化组织进行建模和重塑,不断适应外部刺激来改变其几何形状。基于体内 microCT 的时相形态计量学是研究骨骼(重建)时空动态的有力工具。本文介绍了一种在 12 周龄 BALB/c 裸鼠中检测和量化特定部位骨(重建)差异的方法上的进展。我们描述了我们定量测量新骨表面界面读数的方法,以及这些读数如何受到骨曲率的影响。然后,我们使用该方法比较了不同解剖区域的小鼠的骨表面(重建),以证明其变化率和空间梯度的差异。在骺端和骨干、远端股骨和近端胫骨的皮质骨和松质骨之间,骨(重建)基线参数存在显著差异。使用传统的静态体内 microCT 分析验证了这些结果。最后,这些新的生理骨(重建)基线值的见解被用于评估乳腺癌骨转移模型中的病理性骨(重建)。该方法显示出有潜力用于检测皮质骨和松质骨中的早期病理性事件,并跟踪其时空发展。根据不同的解剖区域对(重建)表面分析和定义基线参数的这种改进,对于研究具有特定部位骨(重建)改变的各种疾病模型的人来说将是有价值的。

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