Department of Biomedical Engineering, Eindhoven University of Technology, PO Box 513, 5600 MB, Eindhoven, The Netherlands.
Biomech Model Mechanobiol. 2011 Oct;10(5):663-70. doi: 10.1007/s10237-010-0264-0. Epub 2010 Nov 11.
Bone formation responds to mechanical loading, which is believed to be mediated by osteocytes. Previous theories assumed that loading stimulates osteocytes to secrete signals that stimulate bone formation. In computer simulations this 'stimulatory' theory successfully produced load-aligned trabecular structures. In recent years, however, it was discovered that osteocytes inhibit bone formation via the protein sclerostin. To reconcile this with strain-induced bone formation, one must assume that sclerostin secretion decreases with mechanical loading. This leads to a new 'inhibitory' theory in which loading inhibits osteocytes from inhibiting bone formation. Here we used computer simulations to show that a sclerostin-based model is able to produce a load-aligned trabecular architecture. An important difference appeared when we compared the response of the stimulatory and inhibitory models to loss of osteocytes, and found that the inhibitory pathway prevents the loss of trabeculae that is seen with the stimulatory model. Further, we demonstrated with combined stimulatory/inhibitory models that the two pathways can work side-by-side to achieve a load-adapted bone architecture.
骨形成对机械加载有响应，据信这种响应是由骨细胞介导的。先前的理论假设，加载刺激骨细胞分泌信号，从而刺激骨形成。在计算机模拟中，这种“刺激”理论成功地产生了与负载对齐的小梁结构。然而，近年来，人们发现骨细胞通过蛋白硬化素抑制骨形成。为了将这一点与应变诱导的骨形成相协调，人们必须假设硬化素的分泌随着机械加载而减少。这就引出了一个新的“抑制”理论，即加载抑制骨细胞抑制骨形成。在这里，我们使用计算机模拟表明，基于硬化素的模型能够产生与负载对齐的小梁结构。当我们比较刺激和抑制模型对骨细胞缺失的反应时，出现了一个重要的差异，我们发现抑制途径可以防止刺激模型中观察到的小梁丢失。此外，我们还通过联合刺激/抑制模型证明，这两种途径可以协同工作，以实现适应负载的骨骼结构。
