4.5 Article

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

Journal

CLINICAL ORAL IMPLANTS RESEARCH
Volume 22, Issue 4, Pages 382-389

Publisher

WILEY
DOI: 10.1111/j.1600-0501.2010.02104.x

Keywords

guided bone regeneration; skeletogenesis; Tgf beta; Bmp signalling; transcriptome; Wnt signalling

Funding

  1. ITI Foundation, Basel, Switzerland

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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 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. 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 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.

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