Transcriptional profiling of cortical versus cancellous bone from mechanically-loaded murine tibiae reveals differential gene expression
Transcriptional profiling of cortical versus cancellous bone from mechanically-loaded murine tibiae reveals differential gene expression
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DOI：
10.1016/j.bone.2016.02.007
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发表时间：
2016-05-01
期刊：
影响因子：
4.1
通讯作者：
van der Meulen, Marjolein C. H.
中科院分区：
文献类型：
--
作者：
Kelly, Natalie H.;Schimenti, John C.;van der Meulen, Marjolein C. H.
机械负荷是一种增加骨量的合成代谢刺激，因此是一种有前途的方法来抵消骨质疏松相关的骨丢失。这种粘连的机制尚不清楚，需要分别建立皮质和松质包膜。我们假设皮质骨和松质骨在基线和对机械负荷的反应中显示不同的基因表达谱。为了检验这一假设，对10周龄雌性C57B16小鼠的左胫骨进行一次轴向胫骨压缩（9 N，1200次循环，4 Hz三角波形），并在加载后3小时和24小时实施安乐死。右侧肢体作为对侧对照。我们对来自皮质骨壳和松质骨核心的无骨髓干骺端样本进行了RNA测序，以确定基线（对照肢体）和对负荷的响应时的差异基因表达。用qPCR验证差异表达。皮质骨和松质骨表现出明显不同的转录谱的基础上，并在响应机械负荷。在两种组织中，在24 h负荷下差异表达的基因更多，在24 h比3 h下调的基因更多。增强的Wnt信号在3和24 h的皮质骨中占主导地位，但仅在3 h的松质骨中占主导地位。在松质骨中，24 h时许多肌肉相关基因表达下调。这些发现揭示了皮质骨和松质骨对机械负荷的遗传调控之间的关键差异。未来在不同时间点和多个负荷会话的研究将增加我们对皮质和松质骨力学转导的了解，并有可能为小鼠基因敲除研究和治疗骨质疏松症的药物确定新的靶点。（C）2016 Elsevier Inc. All rights reserved.
Mechanical loading is an anabolic stimulus that increases bone mass, and thus a promising method to counteract osteoporosis-related bone loss. The mechanism of this anabolism remains unclear, and needs to be established for both cortical and cancellous envelopes individually. We hypothesized that cortical and cancellous bone display different gene expression profiles at baseline and in response to mechanical loading. To test this hypothesis, the left tibiae of 10-week-old female C57B16 mice were subjected to one session of axial tibial compression (9 N, 1200 cycles, 4 Hz riangle waveform) and euthanized 3 and 24 h following loading. The right limb served as the contralateral control. We performed RNA-seq on marrow-free metaphyseal samples from the cortical shell and the cancellous core to determine differential gene expression at baseline (control limb) and in response to load. Differential expression was verified with qPCR. Cortical and cancellous bone exhibited distinctly different transcriptional profiles basally and in response to mechanical loading. More genes were differentially expressed with loading at 24 h with more genes downregulated at 24 h than at 3 h in both tissues. Enhanced Wnt signaling dominated the response in cortical bone at 3 and 24 h, but in cancellous bone only at 3 h. In cancellous bone at 24 h many muscle-related genes were downregulated. These findings reveal key differences between cortical and cancellous genetic regulation in response to mechanical loading. Future studies at different time points and multiple loading sessions will add to our knowledge of cortical and cancellous mechanotransduction with the potential to identify new targets for mouse genetic knockout studies and drugs to treat osteoporosis. ( C) 2016 Elsevier Inc. All rights reserved.