Odontoblast-targeted Bcl-2 overexpression impairs dentin formation.
Apoptosis has been described extensively in tooth development, which is under tight control of multiple apoptosis regulators, including anti-apoptotic protein Bcl-2. However, it is totally unclear how Bcl-2 is related to odontogenesis, especially dentinogenesis. Using a transgenic mouse Col2.3Bcl-2 in which human Bcl-2 was overexpressed in odontoblasts, the effect of Bcl-2 on dentinogenesis was investigated. Overexpression of Bcl-2 was detected by immunohistochemistry and Western blot. Odontoblast apoptosis was evaluated by TUNEL and Western blot detection of cleaved caspase-3. Odontoblast differentiation was assessed by real-time PCR detection of dentin matrix expression. Dentin mineralization was evaluated by micro-CT in vivo, and alizarin red S staining and calcium content analysis in vitro. Bcl-2 was found to be overexpressed in odontoblasts and prevent their apoptosis. Odontoblast differentiation and mineralization was inhibited by Bcl-2, as evidenced by lower expressions of DMP-1, OC, and DSPP, and decreased odontoblast mineralization in vitro, as well as decreased dentin thickness and mineral density in vivo when compared to the wild-type animals. Inhibition of odontoblast differentiation by Bcl-2 occurs, at least partially, via a suppression of MEK-ERK1/2 signaling pathway. In conclusion, Bcl-2 overexpression prevents odontoblast apoptosis and impairs dentin formation, partially via an inhibition of odontoblast differentiation. This study revealed some novel functions of Bcl-2 in dentinogenesis in addition to its anti-apoptotic effect, which shed some light on the genetic complexity of tooth development.
Department of Diagnostic Sciences, University of Texas Dental Branch at Houston, Houston, Texas 77030, USA. wenjian.zhang@uth.tmc.edu
Wenjian
W
Zhang
Jun
J
Ju
Gloria
G
Gronowicz
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003810:Dentinogenesis / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods; D019254:Genes, bcl-2; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009804:Odontoblasts / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology
D019253:Proto-Oncogene Proteins c-bcl-2