Knothe Tate M L, Steck R, Forwood M R, Niederer P
Institute of Biomedical Engineering and Medical Informatics, University and Swiss Federal Institute of Technology, Gloriastrasse 35/ETZ, CH-8092 Zurich, Switzerland.
J Exp Biol. 2000 Sep;203(Pt 18):2737-45. doi: 10.1242/jeb.203.18.2737.
Load-induced extravascular fluid flow has been postulated to play a role in mechanotransduction of physiological loads at the cellular level. Furthermore, the displaced fluid serves as a carrier for metabolites, nutrients, mineral precursors and osteotropic agents important for cellular activity. We hypothesise that load-induced fluid flow enhances the transport of these key substances, thus helping to regulate cellular activity associated with processes of functional adaptation and remodelling. To test this hypothesis, molecular tracer methods developed previously by our group were applied in vivo to observe and quantify the effects of load-induced fluid flow under four-point-bending loads. Preterminal tracer transport studies were carried out on 24 skeletally mature Sprague Dawley rats. Mechanical loading enhanced the transport of both small- and larger-molecular-mass tracers within the bony tissue of the tibial mid-diaphysis. Mechanical loading showed a highly significant effect on the number of periosteocytic spaces exhibiting tracer within the cross section of each bone. For all loading rates studied, the concentration of Procion Red tracer was consistently higher in the tibia subjected to pure bending loads than in the unloaded, contralateral tibia. Furthermore, the enhancement of transport was highly site-specific. In bones subjected to pure bending loads, a greater number of periosteocytic spaces exhibited the presence of tracer in the tension band of the cross section than in the compression band; this may reflect the higher strains induced in the tension band compared with the compression band within the mid-diaphysis of the rat tibia. Regardless of loading mode, the mean difference between the loaded side and the unloaded contralateral control side decreased with increasing loading frequency. Whether this reflects the length of exposure to the tracer or specific frequency effects cannot be determined by this set of experiments. These in vivo experimental results corroborate those of previous ex vivo and in vitro studies. Strain-related differences in tracer distribution provide support for the hypothesis that load-induced fluid flow plays a regulatory role in processes associated with functional adaptation.
负荷诱导的血管外液流被认为在细胞水平的生理负荷机械转导中发挥作用。此外，被置换的液体充当代谢物、营养物质、矿物质前体和对细胞活动重要的促骨生成因子的载体。我们假设负荷诱导的液流增强了这些关键物质的运输，从而有助于调节与功能适应和重塑过程相关的细胞活动。为了验证这一假设，我们小组先前开发的分子示踪方法被应用于体内，以观察和量化四点弯曲负荷下负荷诱导的液流的影响。对24只骨骼成熟的Sprague Dawley大鼠进行了终末前示踪剂运输研究。机械负荷增强了胫骨干中段骨组织内小分子和大分子质量示踪剂的运输。机械负荷对每根骨横截面上显示示踪剂的骨膜细胞间隙数量有非常显著的影响。对于所有研究的负荷率，经受纯弯曲负荷的胫骨中Procion Red示踪剂的浓度始终高于未负荷的对侧胫骨。此外，运输的增强具有高度的位点特异性。在经受纯弯曲负荷的骨骼中，与横截面的压缩带相比，更多的骨膜细胞间隙在横截面的张力带中显示有示踪剂；这可能反映了与大鼠胫骨干中段压缩带相比，张力带中诱导的应变更高。无论负荷模式如何，负荷侧与未负荷对侧对照侧之间的平均差异随着负荷频率的增加而减小。这组实验无法确定这是反映了示踪剂暴露的时间还是特定的频率效应。这些体内实验结果证实了先前的体外和离体研究结果。示踪剂分布中与应变相关的差异为负荷诱导的液流在与功能适应相关的过程中起调节作用这一假设提供了支持。
