title: Odontoblast-targeted Bcl-2 overexpression promotes dentine damage repair.
abstract: OBJECTIVE
  Bcl-2 is widely expressed in a developing tooth organ and regulates tooth morphogenesis. However, whether Bcl-2 is related to tooth damage repair is unknown yet. Using an odontoblast-targeted Bcl-2 overexpression transgenic mouse (Col2.3Bcl-2) and artificial cavity preparation as a model system, the relationship between Bcl-2 and reparative dentinogenesis is investigated in this study.
  
  
  METHODS
  The odontoblastic-like cell cultures derived from mouse molar pulps were established. The expression of transgenic human Bcl-2 (hBcl-2) and endogenous mouse Bcl-2 (mBcl-2) and mouse Bax (mBax, a Bcl-2 antagonist) was detected in vivo and in vitro by Western blot and immunocytochemistry, respectively. Basal level and artificial cavity-induced odontoblast apoptosis was detected by the Deoxynucleotidyl Transferase (TdT) dUTP Nick End labelling (TUNEL) technique. Reparative dentine formation induced by artificial cavity drilled to a half dentine thickness on mesial cervical region of mandibular first molars 2, 4, and 6 weeks post-op was evaluated histologically and via micro-CT.
  
  
  RESULTS
  The transgenic hBcl-2 was stably expressed in odontoblasts of the transgenic animals without interference with the expression of mBcl-2 and mBax. Basal level as well as artificial cavity- induced odontoblast apoptosis was prevented by the transgene. Compared to the wild type, the transgenic animals produced reparative dentine with significantly higher mineral density 6 weeks after the operation.
  
  
  CONCLUSIONS
  Bcl-2 overexpression prevents odontoblast apoptosis and promotes dentine damage repair, indicating that genetic manipulation of Bcl-2 may be a novel strategy to maintain the vitality and function of dentine-pulp complex under detrimental mechanical stimuli.
authors.affiliation: Department of Diagnostic Sciences, University of Texas School of Dentistry at Houston, 77030, USA. Wenjian.Zhang@uth.tmc.edu
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Ju
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D003731:Dental Caries / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003782:Dental Pulp / Q000378:metabolism* / Q000473:pathology; D003809:Dentin, Secondary / Q000378:metabolism*; D003810:Dentinogenesis / Q000235:genetics / Q000502:physiology*; D019254:Genes, bcl-2; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D009804:Odontoblasts / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2