Introduction

Mechanical stimulation of bone is necessary to maintain its mass and architecture. Osteocytes within the mineralized matrix are sensors of mechanical deformation of the hard tissue, and communicate with cells in the marrow to regulate bone remodeling. However, marrow cells are also subjected to mechanical stress during whole bone loading, and may contribute to mechanically regulated bone physiology. Previous results from our laboratory suggest that mechanotransduction in marrow cells is sufficient to cause bone formation in the absence of osteocyte signaling. In this study, we investigated whether bone formation and altered marrow cell gene expression response to stimulation was dependent on the shear stress imparted on the marrow by our loading regime.

Methods

Porcine trabecular bone explants were cultured in an in situ bioreactor for 5 or 28 days with stimulation twice daily. Gene expression and bone formation were quantified and compared to unstimulated controls. Correlation was used to assess the dependence on shear stress imparted by the loading regime calculated using computational fluid dynamics models.

Results

Vibratory stimulation resulted in a higher trabecular bone formation rate (p = 0.01) and a greater increase in bone volume fraction (p = 0.02) in comparison to control explants. Marrow cell expression of cFos increased with the calculated marrow shear stress in a dose-dependent manner (p = 0.002).

Conclusions

The results suggest that the shear stress due to interactions between marrow cells induces a mechanobiological response. Identification of marrow cell mechanotransduction pathways is essential to understand healthy and pathological bone adaptation and remodeling.

中文翻译：

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骨髓中的剪切应力对原位培养中的 cFos 基因表达具有剂量依赖性影响

介绍

骨骼的机械刺激对于维持其质量和结构是必要的。矿化基质中的骨细胞是硬组织机械变形的传感器，并与骨髓中的细胞交流以调节骨重塑。然而，骨髓细胞在全骨负荷期间也会受到机械应力，并且可能有助于机械调节骨生理学。我们实验室以前的结果表明，骨髓细胞中的机械转导足以在没有骨细胞信号传导的情况下引起骨形成。在这项研究中，我们研究了骨形成和改变的骨髓细胞基因表达对刺激的反应是否取决于我们的加载方案赋予骨髓的剪切应力。

方法

猪小梁骨外植体在原位生物反应器中培养 5 或 28 天，每天刺激两次。量化基因表达和骨形成并与未刺激的对照进行比较。相关性用于评估使用计算流体动力学模型计算的加载方案对剪切应力的依赖性。

结果

 与对照外植体相比，振动刺激导致更高的骨小梁形成率 ( p  = 0.01) 和更大的骨体积分数增加 ( p = 0.02)。cFos 的骨髓细胞表达随着计算的骨髓剪切应力以剂量依赖性方式增加（p  = 0.002）。

结论

结果表明，由于骨髓细胞之间的相互作用引起的剪切应力诱导了机械生物学反应。鉴定骨髓细胞机械转导途径对于了解健康和病理性骨适应和重塑至关重要。