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Odontoblast‐targeted Bcl‐2 overexpression impairs dentin formation
Author(s) -
Zhang Wenjian,
Ju Jun,
Gronowicz Gloria
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22722
Subject(s) - odontoblast , dentinogenesis , dentin sialophosphoprotein , apoptosis , dentin , chemistry , tunel assay , microbiology and biotechnology , western blot , in vivo , biology , pathology , biochemistry , medicine , gene , genetics
Abstract 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. J. Cell. Biochem. 111: 425–432, 2010. © 2010 Wiley‐Liss, Inc.