Stavenschi Elena, Labour Marie-Noelle, Hoey David A
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Dept. of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland.
Trinity Centre for Bioengineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland; Dept. of Mechanical and Manufacturing Engineering, School of Engineering, Trinity College Dublin, Dublin 2, Ireland; Dept. of Mechanical, Aeronautical and Biomedical Engineering, University of Limerick, Ireland; Advanced Materials and Bioengineering Research Centre, Trinity College Dublin & RCSI, Dublin 2, Ireland.
J Biomech. 2017 Apr 11;55:99-106. doi: 10.1016/j.jbiomech.2017.02.002. Epub 2017 Feb 21.
A potent regulator of bone anabolism is physical loading. However, it is currently unclear whether physical stimuli such as fluid shear within the marrow cavity is sufficient to directly drive the osteogenic lineage commitment of resident mesenchymal stem cells (MSC). Therefore, the objective of the study is to employ a systematic analysis of oscillatory fluid flow (OFF) parameters predicted to occur in vivo on early MSC osteogenic responses and late stage lineage commitment. MSCs were exposed to OFF of 1Pa, 2Pa and 5Pa magnitudes at frequencies of 0.5Hz, 1Hz and 2Hz for 1h, 2h and 4h of stimulation. Our findings demonstrate that OFF elicits a positive osteogenic response in MSCs in a shear stress magnitude, frequency, and duration dependent manner that is gene specific. Based on the mRNA expression of osteogenic markers Cox2, Runx2 and Opn after short-term fluid flow stimulation, we identified that a regime of 2Pa shear magnitude and 2Hz frequency induces the most robust and reliable upregulation in osteogenic gene expression. Furthermore, long-term mechanical stimulation utilising this regime, elicits a significant increase in collagen and mineral deposition when compared to static control demonstrating that mechanical stimuli predicted within the marrow is sufficient to directly drive osteogenesis.
骨骼合成代谢的一个重要调节因素是身体负荷。然而，目前尚不清楚诸如骨髓腔内的流体剪切力等物理刺激是否足以直接驱动驻留间充质干细胞（MSC）的成骨谱系定向分化。因此，本研究的目的是对预计在体内发生的振荡流体流动（OFF）参数进行系统分析，以研究其对早期MSC成骨反应和晚期谱系定向分化的影响。将MSC暴露于1Pa、2Pa和5Pa强度的OFF下，频率分别为0.5Hz、1Hz和2Hz，刺激时间分别为1小时、2小时和4小时。我们的研究结果表明，OFF以剪切应力强度、频率和持续时间依赖的方式在MSC中引发阳性成骨反应，且具有基因特异性。基于短期流体流动刺激后成骨标志物Cox2、Runx2和Opn的mRNA表达，我们发现2Pa剪切强度和2Hz频率的条件诱导成骨基因表达上调最为强烈和可靠。此外，与静态对照相比，利用该条件进行长期机械刺激会导致胶原蛋白和矿物质沉积显著增加，这表明骨髓内预计的机械刺激足以直接驱动骨生成。
