Real-time measurement of solute transport within the lacunar-canalicular system of mechanically loaded bone: direct evidence for load-induced fluid flow.
Real-time measurement of solute transport within the lacunar-canalicular system of mechanically loaded bone: direct evidence for load-induced fluid flow.
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DOI：
10.1002/jbmr.211
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发表时间：
2011-02
影响因子：
6.2
通讯作者：
Wang, Liyun
中科院分区：
文献类型：
--
作者：
Price, Christopher;Zhou, Xiaozhou;Li, Wen;Wang, Liyun
自1977年Piekarski和Munro提出载荷诱导的液体通过骨腔隙-管系统（LCS）以来，已被认为是骨代谢、机械转导和适应的关键。然而，由于技术上的困难，一直缺乏通过LCS对负载引起的流体和溶质对流进行直接明确的观察和量化。采用基于光漂白后荧光恢复（FRAP）和同步机械加载和成像的新实验方法，我们成功地定量了小荧光示踪剂（荧光素钠，376 Da）在成年雄性C57BL/6J小鼠骨LCS中的扩散和对流输运。我们证明，与单独扩散相比，中等负荷（-3 N峰值负荷或0.5 Hz时400 μ /表面应变）的小鼠胫骨循环末端压缩和相邻负荷周期之间插入4秒休息/成像窗口可显著增强荧光素钠通过LCS的转运（+31%）。使用基于解剖学的三室运输模型，预测了加载骨中的峰值管流体速度（60µm/s），并估计了骨细胞过程膜上产生的峰值剪切应力（~ 5 Pa）。这项研究令人信服地证明了在机械载荷骨中存在载荷诱导对流。本文提出的实验与数学相结合的方法代表了在原位骨细胞所经历的微流体环境量化方面的重要进展，并为进一步研究机械刺激调节骨细胞反应的机制奠定了基础，这将为基础骨生物学，骨质疏松症和骨质流失的临床理解以及其治疗的合理工程提供信息。©2011美国骨与矿物研究学会。
Since proposed by Piekarski and Munro in 1977, load-induced fluid flow through the bone lacunar-canalicular system (LCS) has been accepted as critical for bone metabolism, mechanotransduction, and adaptation. However, direct unequivocal observation and quantification of load-induced fluid and solute convection through the LCS have been lacking due to technical difficulties. Using a novel experimental approach based on fluorescence recovery after photobleaching (FRAP) and synchronized mechanical loading and imaging, we successfully quantified the diffusive and convective transport of a small fluorescent tracer (sodium fluorescein, 376 Da) in the bone LCS of adult male C57BL/6J mice. We demonstrated that cyclic end-compression of the mouse tibia with a moderate loading magnitude (–3 N peak load or 400 µɛ surface strain at 0.5 Hz) and a 4-second rest/imaging window inserted between adjacent load cycles significantly enhanced (+31%) the transport of sodium fluorescein through the LCS compared with diffusion alone. Using an anatomically based three-compartment transport model, the peak canalicular fluid velocity in the loaded bone was predicted (60 µm/s), and the resulting peak shear stress at the osteocyte process membrane was estimated (∼5 Pa). This study convincingly demonstrated the presence of load-induced convection in mechanically loaded bone. The combined experimental and mathematical approach presented herein represents an important advance in quantifying the microfluidic environment experienced by osteocytes in situ and provides a foundation for further studying the mechanisms by which mechanical stimulation modulates osteocytic cellular responses, which will inform basic bone biology, clinical understanding of osteoporosis and bone loss, and the rational engineering of their treatments. © 2011 American Society for Bone and Mineral Research.
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