title: Transcriptional profiling of "guided bone regeneration" in a critical-size calvarial defect.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: School of Dentistry and Oral Health, Centre for Medicine and Oral Health, Griffith University, Gold Coast Campus, Qld, Australia. s.ivanovski@griffith.edu.au
authors.forename: S
authors.initials: S
authors.lastname: Ivanovski
authors.forename: S
authors.initials: S
authors.lastname: Hamlet
authors.forename: M
authors.initials: M
authors.lastname: Retzepi
authors.forename: I
authors.initials: I
authors.lastname: Wall
authors.forename: N
authors.initials: N
authors.lastname: Donos
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D001861:Bone Regeneration / Q000235:genetics*; D020869:Gene Expression Profiling; D016557:Guided Tissue Regeneration, Periodontal; D020007:Implants, Experimental; D020411:Oligonucleotide Array Sequence Analysis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics; D012886:Skull / Q000601:surgery; D013997:Time Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D015854:Up-Regulation; D051153:Wnt Proteins / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D016283:Proto-Oncogene Proteins p21(ras); D020741:rho GTP-Binding Proteins