Institute for Biomechanics, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland.
Bone. 2013 Mar;53(1):14-23. doi: 10.1016/j.bone.2012.11.017. Epub 2012 Nov 28.
Osteocytes are considered the skeletal mechanosensors. However, because osteocytes, particularly trabecular, are barely accessible to in vivo molecular analyses, very little is known on the signals transmitted by these cells to the extra-trabecular milieu. To investigate so called "osteocytic genes" involved in extracellular signaling, we have used a recently developed model whereby a single caudal mouse vertebra (C5) is subjected to controlled compression loading and further devised a method for the isolation of high quality RNA from trabecular osteocytes. RNA samples from loaded and sham-loaded individual vertebrae where then subjected to gene array analysis following the administration of a single or repetitive loading doses (thrice weekly for 4 weeks). Focusing on extracellular genes potentially involved in mediating osteocyte-derived signals to the trabecular surface, we identified sets of genes differentially regulated by either single or multiple loading bouts as well as genes affected by both loading protocols. A comparison with published studies on load-regulated genes in cortical osteocytes revealed that the majority of these genes are specifically activated/silenced in the trabecular bone. Many of these genes could be clustered according to processes directly relevant to the life cycle and activity of osteoblasts and osteoclasts and their progenitors. The present findings are consistent with an osteocytic role in the control of trabecular bone remodeling and mass and provide a comprehensive database of load-regulated genes in trabecular osteocytes that is potentially useful in further mouse genetic studies and identification of drug targets to combat osteoporosis.
成骨细胞被认为是骨骼的机械感受器。然而，由于成骨细胞，特别是小梁骨的成骨细胞，几乎无法进行体内分子分析，因此对于这些细胞向小梁外环境传递的信号知之甚少。为了研究参与细胞外信号传递的所谓“成骨细胞基因”，我们使用了一种最近开发的模型，即对单个尾骨（C5）进行受控压缩加载，并且进一步设计了一种从小梁成骨细胞中分离高质量 RNA 的方法。然后对加载和假加载的个体椎骨的 RNA 样本进行基因芯片分析，随后进行单次或重复加载剂量（每周 3 次，持续 4 周）的基因表达分析。我们关注的是潜在参与介导骨细胞衍生信号到小梁表面的细胞外基因，我们确定了由单次或多次加载冲击差异调节的基因集，以及受两种加载方案影响的基因。与皮质成骨细胞中负荷调节基因的已发表研究进行比较表明，这些基因中的大多数在小梁骨中特异性激活/沉默。根据与成骨细胞和破骨细胞及其祖细胞的生命周期和活性直接相关的过程，许多基因可以聚类。这些发现与成骨细胞在控制小梁骨重塑和骨量中的作用一致，并为小梁成骨细胞中的负荷调节基因提供了一个全面的数据库，这对于进一步的小鼠遗传研究和骨质疏松症药物靶点的鉴定可能是有用的。
