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在临界尺寸颅骨缺损中“引导骨再生”的转录谱分析。

Transcriptional profiling of "guided bone regeneration" in a critical-size calvarial defect.

机构信息

School of Dentistry and Oral Health, Centre for Medicine and Oral Health, Griffith University, Gold Coast Campus, Qld, Australia.

出版信息

Clin Oral Implants Res. 2011 Apr;22(4):382-9. doi: 10.1111/j.1600-0501.2010.02104.x.

DOI:10.1111/j.1600-0501.2010.02104.x
PMID:21561480
Abstract

OBJECTIVES

Guided 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 METHODS

Critical-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.

RESULTS

Gene 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 Tgfβ/Bmp and Wnt signalling were also up-regulated. Besides skeletogenesis, genes associated with angiogenesis and neurogenesis were also up-regulated at day 14.

CONCLUSIONS

The 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 Tgfβ/Bmp and Wnt signalling pathways play an important role in the regenerative process.

摘要

目的

引导骨再生(GBR)是一种常用于头面部区域的外科技术。与这种类型的骨再生相关的转录机制尚不清楚。本研究的目的是描述与大鼠临界尺寸颅骨缺损 GBR 相关的转录组特征。

材料和方法

在六只 Wistar 大鼠中创建临界尺寸颅骨缺损,并根据 GBR 原则进行治疗。在 7 天和 14 天采集填充再生缺损的组织。提取总 RNA 并进行微阵列分析,以确定 7 天和 14 天之间转录组的差异。

结果

第 7 天上调基因的基因本体论(GO)分析表明,不成熟的伤口愈合相关机制,如蛋白质代谢和细胞增殖,在此时间点上调。此外,免疫炎症过程也在早期上调。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,上调。此外,与骨骼发育、骨化和骨矿化相关的功能重要 GO 类别在第 14 天上调。属于这一组并在第 14 天上调的感兴趣基因包括生长和分化因子(Bmp2、Bmp3、Tgfb3)、细胞外基质蛋白(骨钙素、骨调节素、Stenniocalcin 1)和转录因子(Runx2、Sox6、Satb2)。此外,许多与 TGFβ/Bmp 和 Wnt 信号相关的基因也上调。除了骨骼发生外,与血管生成和神经发生相关的基因也在第 14 天上调。

结论

成熟 GBR 治疗的头面部骨缺损相关的转录组特征是免疫炎症反应下调,骨骼发生、血管生成和神经发生相关基因上调。TGFβ/Bmp 和 Wnt 信号通路在再生过程中发挥重要作用。

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