Gene expression patterns in bone following mechanical loading.

Gene expression patterns in bone following mechanical loading.
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DOI:
10.1002/jbmr.193
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发表时间:
2011-01
影响因子:
6.2
通讯作者:
Turner, Charles H.
Turner, Charles H.
中科院分区:
医学1区
文献类型:
--
作者:
Roosa, Sara M. Mantila;Liu, Yunlong;Turner, Charles H.

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基因表达的高通量测量和生物信息学分析方法的出现为研究基因表达模式提供了新的途径。本研究的主要目的是确定骨形成过程中关键时期机械负荷下骨中基因表达的时间顺序,包括基质相关基因的表达、活性成骨细胞的出现和骨脱敏。骨负荷的标准模型,其中右前肢轴向负荷3分钟,每天,而左前臂作为一个非负载对侧控制。我们评估了第一次加载后4小时至32天的时间过程中加载诱导的基因表达。六个不同的时间依赖性模式的基因表达的时间过程中被确定,并被分为三个主要集群:基因上调早在时间过程中,基因上调基质形成过程中,和基因下调基质形成。然后根据功能和/或信号通路对基因进行分组。许多已知在负荷诱导的骨形成中重要的基因组在簇中被鉴定,包括早期反应簇中的AP-1相关基因、上调基因簇中的基质相关基因和下调基因簇中的Wnt/β-连环蛋白信号通路抑制剂。几个新的基因组也被确定,包括趋化因子相关的基因,这是上调早期,但下调后的时间过程中;溶质载体基因,这是上调和下调;和肌肉相关的基因,主要是下调。© 2011美国骨与矿物质研究学会。
The advent of high-throughput measurements of gene expression and bioinformatics analysis methods offers new ways to study gene expression patterns. The primary goal of this study was to determine the time sequence for gene expression in a bone subjected to mechanical loading during key periods of the bone-formation process, including expression of matrix-related genes, the appearance of active osteoblasts, and bone desensitization. A standard model for bone loading was employed in which the right forelimb was loaded axially for 3 minutes per day, whereas the left forearm served as a nonloaded contralateral control. We evaluated loading-induced gene expression over a time course of 4 hours to 32 days after the first loading session. Six distinct time-dependent patterns of gene expression were identified over the time course and were categorized into three primary clusters: genes upregulated early in the time course, genes upregulated during matrix formation, and genes downregulated during matrix formation. Genes then were grouped based on function and/or signaling pathways. Many gene groups known to be important in loading-induced bone formation were identified within the clusters, including AP-1-related genes in the early-response cluster, matrix-related genes in the upregulated gene clusters, and Wnt/β-catenin signaling pathway inhibitors in the downregulated gene clusters. Several novel gene groups were identified as well, including chemokine-related genes, which were upregulated early but downregulated later in the time course; solute carrier genes, which were both upregulated and downregulated; and muscle-related genes, which were primarily downregulated. © 2011 American Society for Bone and Mineral Research.
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