Gene expression dynamics during bone healing and osseointegration

J Periodontol. 2011 Jul;82(7):1007-17. doi: 10.1902/jop.2010.100577. Epub 2010 Dec 13.

Abstract

Background: Understanding the molecular features of bone repair and osseointegration may aid in the development of therapeutics to improve implant outcomes. The purpose of this investigation is to determine the gene expression dynamics during alveolar bone repair and implant osseointegration.

Methods: An implant osseointegration preclinical animal model was used whereby maxillary defects were created at the time of oral implant placement, while a tooth extraction socket healing model was established on the contralateral side of each animal. The surrounding tissues in the zone of the healing defects were harvested during regeneration for temporal evaluation using histology, immunohistochemistry, laser capture microdissection, and quantitative reverse transcription-polymerase chain reaction for the identification of a panel of 17 putative genes associated with wound repair.

Results: In both models, three distinct expression patterns were displayed: 1) genes that are slowly increased during the healing process, such as bone morphogenetic protein 4, runt-related transcription factor 2, and osteocalcin; 2) genes that are upregulated at the early stage of healing and then downregulated at later stages, such as interleukin and chemokine (C-X-C motif) ligands 2 and 5; and 3) genes that are constitutively expressed over time, such as scleraxis. Although some similarities between osseointegration and tooth extraction socket were seen, distinct features developed and triggered a characteristic coordinated expression and orchestration of transcription factors, growth factors, extracellular matrix molecules, and chemokines.

Conclusions: Characterization of these events contributes to a better understanding of cooperative molecular dynamics in alveolar bone healing, and highlights potential pathways that could be further explored for the enhancement of osseous regenerative strategies.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alveolar Process / pathology
  • Alveolar Process / physiopathology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Regeneration / genetics*
  • Cell Adhesion Molecules / genetics
  • Chemokine CXCL2 / genetics
  • Chemokine CXCL5 / genetics
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Dental Implantation, Endosseous
  • Dental Implants
  • Disease Models, Animal
  • Gene Expression Regulation / genetics
  • Immunohistochemistry
  • Interleukins / genetics
  • Male
  • Maxilla / surgery
  • Microdissection / methods
  • Osseointegration / genetics*
  • Osteocalcin / genetics
  • Osteotomy / methods
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tooth Extraction
  • Tooth Socket / pathology
  • Tooth Socket / physiopathology
  • Transforming Growth Factor beta1 / genetics
  • Wound Healing / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Bmp4 protein, rat
  • Bone Morphogenetic Protein 4
  • Cell Adhesion Molecules
  • Chemokine CXCL2
  • Chemokine CXCL5
  • Core Binding Factor Alpha 1 Subunit
  • Cxcl2 protein, rat
  • Dental Implants
  • Interleukins
  • Postn protein, rat
  • Runx2 protein, rat
  • Scx protein, rat
  • Transforming Growth Factor beta1
  • Osteocalcin