Navigation of osteoblasts in the bone space

骨形成，例如在骨生长或重塑期间，取决于成骨细胞迁移到骨形成的指定区域的能力。因此，提出了一个基本的问题：成骨细胞如何导航到骨空间内的适当位置？已知它们通过整合素附着于细胞外基质，并且它们可以以化学引诱物依赖性方式迁移。然而，由于有限的特异性和已知的趋化因子的数量，这是不太可能的趋化性单独允许导航。因此，我们的基本假设是，生物物理和细胞信号的相互作用为导航提供了坐标。我们计划在单细胞水平上实时研究原代成骨细胞的动力学。对于目标1，我们假设骨表面为成骨细胞提供基本的导航信号，而目标2将测试两方或三方细胞相互作用为成骨细胞提供额外导航坐标的假设。在目标3中，我们将测试定向、局部流体流动是否可作为成骨细胞导航的标志。总之，这些研究有望揭示成骨细胞用于导航的去/停信号。结果将导致扩展研究解决控制这些信号的途径。拟议的研究的长期影响是深远的，在肌肉骨骼研究的许多方面，如骨组织工程，代谢性骨病和骨骼癌的影响。

Bone formation, for example during bone growth or remodeling, depends on the capacity of osteoblasts for migration to designated areas of bone formation. Thus, posing the fundamental question: How do osteoblasts navigate to the appropriate position within the bone space? It is known that they attach to the extracellular matrix via integrins and that they can migrate in a chemoattractant-dependent fashion. However, given limited specificity and number of known chemoattractans, it is unlikely that chemotaxis alone permits navigation. Therefore, our underlying hypothesis is that the interplay of biophysical and cellular signals provides coordinates for navigation. We plan on studying the kinetics of primary osteoblasts on the single cell level in real-time. For Aim 1, we hypothesize that osseous surfaces offer basic navigation signals to osteoblasts, while Aim 2 will test the hypothesis that two or three party cell interactions provide additional navigation coordinates for osteoblasts. In Aim 3, we will test if directed, localized fluid flow serves as landmark in osteoblast navigation. Together, these studies are expected to reveal go/stop signals osteoblasts use for navigation. The results will lead to extended studies addressing the pathways controlling such signals. The long term impact of the proposed studies is far-reaching with implications in many aspects of musculoskeletal research, such as bone tissue engineering, metabolic bone disease, and skeletal cancer.