Document Detail


Odontoblast-targeted Bcl-2 overexpression impairs dentin formation.
MedLine Citation:
PMID:  20518070     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Wenjian Zhang; Jun Ju; Gloria Gronowicz
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  111     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-27     Completed Date:  2011-01-25     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  425-32     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Calcification, Physiologic / drug effects
Cell Differentiation / drug effects
Dentinogenesis / drug effects*
Drug Delivery Systems / methods
Genes, bcl-2*
Humans
Mice
Mice, Transgenic
Odontoblasts / drug effects*
Proto-Oncogene Proteins c-bcl-2 / administration & dosage*,  genetics,  pharmacology
Grant Support
ID/Acronym/Agency:
1R03DE019663-01A1/DE/NIDCR NIH HHS; R03 DE019663/DE/NIDCR NIH HHS; R03 DE019663-01A1/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2
Comments/Corrections

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