来自机械刺激骨细胞的细胞外一氧化氮信号传导。
Extracellular NO signalling from a mechanically stimulated osteocyte.
作者信息
Vatsa Aviral, Smit Theo H, Klein-Nulend Jenneke
机构信息
Department of Oral Cell Biology, ACTA-Universiteit van Amsterdam, Vrije Universiteit, Research Institute MOVE, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
出版信息
J Biomech. 2007;40 Suppl 1:S89-95. doi: 10.1016/j.jbiomech.2007.02.015. Epub 2007 May 18.
Bone remodelling is a dynamic process that requires the coordinated interaction of osteocytes, osteoblasts, and osteoclasts, collaborating in basic multicellular units (BMUs). Communication between these cells can be by extracellular soluble molecules as well as directly propagating intercellular signalling molecules. Key to the understanding of bone remodelling is osteocyte mechanosensing and chemical signalling to the surrounding cells, since osteocytes are believed to be the mechanosensors of bone, responding to mechanical stresses. Nitric oxide (NO) is an important parameter to study osteocyte activation following mechanical loading. It is a small short-lived molecule, which makes its real-time, quantitative monitoring difficult. However, recently we demonstrated that DAR-4M AM chromophore can be used for real-time quantitative monitoring of intracellular NO production in individual cells following mechanical loading. Here we studied if a single mechanically stimulated osteocyte communicates with, and thus activates its surrounding cells via extracellular soluble factors. We monitored quantitatively intracellular NO production in the stimulated osteocyte and in its surrounding osteocytes, which were not interconnected. Mechanical stimulation by microneedle of a single-MLO-Y4 osteocyte-like cell upregulated the average intracellular NO production by 94% in the stimulated cell, and by 31-150% in the surrounding osteocytes. In conclusion, a single osteocyte can disseminate a mechanical stimulus to its surrounding osteocytes via extracellular soluble signalling factors. This reinforces the putative mechanosensory role of osteocytes, and demonstrates a possible mechanism by which a single mechanically stimulated osteocyte can communicate with other cells in a BMU, which might help to better understand the intricacies of intercellular interactions in BMUs and thus bone remodelling.
骨重塑是一个动态过程,需要骨细胞、成骨细胞和破骨细胞在基本多细胞单位(BMU)中协同相互作用。这些细胞之间的通讯可以通过细胞外可溶性分子以及直接传播的细胞间信号分子来实现。理解骨重塑的关键在于骨细胞的机械传感以及向周围细胞的化学信号传递,因为骨细胞被认为是骨的机械传感器,对机械应力作出反应。一氧化氮(NO)是研究机械加载后骨细胞激活的一个重要参数。它是一种小的、寿命短的分子,这使得对其进行实时、定量监测变得困难。然而,最近我们证明,DAR-4M AM发色团可用于实时定量监测机械加载后单个细胞内的NO生成。在这里,我们研究了单个受到机械刺激的骨细胞是否通过细胞外可溶性因子与其周围细胞进行通讯,从而激活周围细胞。我们定量监测了受刺激骨细胞及其周围未相互连接的骨细胞内的NO生成。用微针机械刺激单个MLO-Y4类骨细胞,受刺激细胞内的平均NO生成上调了94%,周围骨细胞内上调了31%-150%。总之,单个骨细胞可以通过细胞外可溶性信号因子将机械刺激传递给其周围的骨细胞。这加强了骨细胞假定的机械传感作用,并证明了单个受到机械刺激的骨细胞与BMU中的其他细胞进行通讯的一种可能机制,这可能有助于更好地理解BMU中细胞间相互作用的复杂性,进而更好地理解骨重塑。