Curtis Kimberly J, Coughlin Thomas R, Varsanik Mary A, Niebur Glen L
Tissue Mechanics Laboratory, University of Notre Dame, Notre Dame, IN 46556 USA.
Bioengineering Graduate Program, University of Notre Dame, 147 Multidisciplinary Engineering Research, Notre Dame, IN 46556 USA.
Cell Mol Bioeng. 2019 Aug 27;12(6):559-568. doi: 10.1007/s12195-019-00594-z. eCollection 2019 Dec.
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.
Porcine trabecular bone explants were cultured in an 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.
Vibratory stimulation resulted in a higher trabecular bone formation rate ( = 0.01) and a greater increase in bone volume fraction ( = 0.02) in comparison to control explants. Marrow cell expression of cFos increased with the calculated marrow shear stress in a dose-dependent manner ( = 0.002).
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.
对骨骼进行机械刺激对于维持其质量和结构至关重要。矿化基质中的骨细胞是硬组织机械变形的传感器，并与骨髓中的细胞进行通讯以调节骨重塑。然而，在整个骨骼加载过程中，骨髓细胞也会受到机械应力，并且可能有助于机械调节的骨生理过程。我们实验室之前的结果表明，在没有骨细胞信号传导的情况下，骨髓细胞中的机械转导足以导致骨形成。在本研究中，我们调查了骨形成和骨髓细胞基因表达对刺激的改变反应是否依赖于我们的加载方案施加在骨髓上的剪切应力。
将猪小梁骨外植体在生物反应器中培养5天或28天，每天刺激两次。对基因表达和骨形成进行定量，并与未刺激的对照进行比较。使用相关性来评估对使用计算流体动力学模型计算的加载方案施加的剪切应力的依赖性。
与对照外植体相比，振动刺激导致更高的小梁骨形成率（ = 0.01）和更大的骨体积分数增加（ = 0.02）。cFos的骨髓细胞表达随着计算出的骨髓剪切应力以剂量依赖的方式增加（ = 0.002）。
结果表明，骨髓细胞之间相互作用产生的剪切应力诱导了一种机械生物学反应。识别骨髓细胞机械转导途径对于理解健康和病理性骨适应及重塑至关重要。
