Transcriptional profiling of "guided bone regeneration" in a critical-size calvarial defect
Transcriptional profiling of "guided bone regeneration" in a critical-size calvarial defect
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DOI：
10.1111/j.1600-0501.2010.02104.x
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发表时间：
2011-04-01
影响因子：
4.3
通讯作者：
Donos, N.
中科院分区：
文献类型：
--
作者：
Ivanovski, S.;Hamlet, S.;Donos, N.
目的引导骨再生术（GBR）是颅颌面部常用的外科技术。与这种类型的骨再生相关的转录机制还不清楚。本研究的目的是表征转录组与GBR的一个关键大小的颅骨缺损的大鼠。材料和方法的关键大小的颅骨缺损，在6个Wistar品系大鼠和治疗GBR的原则。在第7天和第14天收获填充再生缺损的组织。提取总RNA，采用基因芯片技术分析第7天和第14天转录组的差异。结果基因本体（GO）分析显示，在第7天表达上调的基因中，与未成熟创面愈合相关的蛋白质代谢和细胞增殖等机制在此时间点表达上调。此外，免疫炎症过程也在较早的时间点上调。相比之下，到第14天，与伤口成熟一致的GO组，如细胞外基质形成、解剖结构发育和细胞分化均上调。此外，功能上重要的骨骼发育、骨化和骨矿化的GO类别在第14天上调。属于该组并且在第14天上调的感兴趣的基因包括生长和分化因子（Bmp 2、Bmp 3、Tgfb 3）、细胞外基质蛋白（骨钙蛋白、骨调节蛋白、stenniocalcin 1）和转录因子（Runx 2、Sox 6、Satb 2）。此外，一些与TGF β/Bmp和Wnt信号传导相关的基因也被上调。结论GBR处理的成熟颅面骨缺损的转录组与免疫炎症反应的下调和骨生成、血管生成和神经发生相关基因的上调有关。TGF β/BMP和Wnt信号通路在再生过程中起着重要作用。引用本文：Ivanovski S，哈姆雷特S，Retzepi M，Wall I，Donos N.关键尺寸颅骨缺损中“引导性骨再生”的转录谱。Res. 22，2011; 382-389.
ObjectivesGuided bone regeneration (GBR) is a commonly utilized surgical technique in the craniofacial region. The transcriptional mechanisms associated with this type of bone regeneration are not well understood. The aim of this study was to characterize the transcriptome associated with GBR of a critical-size calvarial defect in the rat.Material and methodsCritical-size calvarial defects were created in six Wistar strain rats and treated according to the principles of GBR. The tissue filling the regenerating defect was harvested at 7 and 14 days. Total RNA was extracted and microarray analysis was carried out to identify the differences in the transcriptome between days 7 and 14.ResultsGene ontology (GO) analysis of the genes up-regulated at day 7 showed that immature wound healing-related mechanisms, such as protein metabolism and cell proliferation, were up-regulated at this time point. Furthermore, the immuno-inflammatory process was also up-regulated at the earlier time point. In contrast, by day 14, GO groups consistent with wound maturation, such as extracellular matrix formation, anatomical structure development and cell differentiation, were up-regulated. Furthermore, the functionally important GO categories of skeletal development, ossification and bone mineralization were up-regulated at day 14. Genes of interest that belonged to this group and were up-regulated at day 14 included growth and differentiation factors (Bmp2, Bmp3, Tgfb3), extracellular matrix proteins (osteocalcin, osteomodulin, stenniocalcin 1) and transcription factors (Runx2, Sox6, Satb2). Furthermore, a number of genes associated with Tgf beta/Bmp and Wnt signalling were also up-regulated. Besides skeletogenesis, genes associated with angiogenesis and neurogenesis were also up-regulated at day 14.ConclusionsThe transcriptome associated with a maturing GBR-treated craniofacial bone defect is characterized by the down-regulation of the immuno-inflammatory response and up-regulation of skeletogeneis-, angiogenesis- and neurogenesis-associated genes. The Tgf beta/Bmp and Wnt signalling pathways play an important role in the regenerative process.To cite this article:Ivanovski S, Hamlet S, Retzepi M, Wall I, Donos N. Transcriptional profiling of "guided bone regeneration" in a critical size calvarial defect.Clin. Oral Impl. Res. 22, 2011; 382-389.