Differential load-regulated global gene expression in mouse trabecular osteocytes
Differential load-regulated global gene expression in mouse trabecular osteocytes
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DOI：
10.1016/j.bone.2012.11.017
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发表时间：
2013-03-01
期刊：
影响因子：
4.1
通讯作者：
Bab, Itai
中科院分区：
文献类型：
--
作者：
Wasserman, Elad;Webster, Duncan;Bab, Itai
骨细胞被认为是骨骼机械传感器。然而，由于骨细胞，特别是小梁细胞，几乎无法进行体内分子分析，因此对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导的所谓“骨细胞基因”，我们使用了最近开发的模型，使单个尾部小鼠椎骨（C5）受到受控的压缩负载，并进一步设计了一种从小梁骨细胞中分离高质量RNA的方法。来自加载和假加载的单个椎骨的 RNA 样本随后在施用单次或重复加载剂量（每周三次，持续 4 周）后进行基因阵列分析。着眼于可能参与介导骨细胞衍生信号至小梁表面的细胞外基因，我们确定了受单次或多次加载回合差异调节的基因组以及受两种加载方案影响的基因。与已发表的皮质骨细胞负荷调节基因研究的比较表明，这些基因中的大多数在骨小梁中被特异性激活/沉默。许多这些基因可以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进行聚类。目前的研究结果与骨细胞在控制小梁骨重塑和质量中的作用一致，并提供了小梁骨细胞中负荷调节基因的综合数据库，该数据库可能有助于进一步的小鼠遗传学研究和识别抗击骨质疏松症的药物靶点。 (C) 2012 Elsevier Inc. 保留所有权利。
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. (C) 2012 Elsevier Inc. All rights reserved.