title: Gene expression dynamics during bone healing and osseointegration.
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.
authors.affiliation: Division of Periodontology, Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Lin
authors.forename: Hector F
authors.initials: HF
authors.lastname: Rios
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Volk
authors.forename: James V
authors.initials: JV
authors.lastname: Sugai
authors.forename: Qiming
authors.initials: Q
authors.lastname: Jin
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D000539:Alveolar Process / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics; D001861:Bone Regeneration / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics; D054426:Chemokine CXCL2 / Q000235:genetics; D054365:Chemokine CXCL5 / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D003758:Dental Implantation, Endosseous; D015921:Dental Implants; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D007150:Immunohistochemistry; D007378:Interleukins / Q000235:genetics; D008297:Male; D008437:Maxilla / Q000601:surgery; D042282:Microdissection / Q000379:methods; D016348:Osseointegration / Q000235:genetics*; D015675:Osteocalcin / Q000235:genetics; D010027:Osteotomy / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014081:Tooth Extraction; D020390:Tooth Socket / Q000473:pathology / Q000503:physiopathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014945:Wound Healing / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D055415:Bone Morphogenetic Protein 4; D015815:Cell Adhesion Molecules; D054426:Chemokine CXCL2; D054365:Chemokine CXCL5; D050659:Core Binding Factor Alpha 1 Subunit; D015921:Dental Implants; D007378:Interleukins; D015675:Osteocalcin; D053773:Transforming Growth Factor beta1; C525811:Bmp4 protein, rat; C513296:Cxcl2 protein, rat; C512836:Postn protein, rat; C493717:Runx2 protein, rat; C503819:Scx protein, rat