Odontoblast-targeted Bcl-2 overexpression promotes dentine damage repair

Objective 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. s ontoblastic-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. s ansgenic 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. sions 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.