Document Detail


Mandibular phenotype of p20C/EBPbeta transgenic mice: Reduced alveolar bone mass and site-specific dentin dysplasia.
MedLine Citation:
PMID:  16682266     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CCAAT enhancer binding proteins (C/EBP) comprise a family of basic-leucine zipper transcription factors that regulate cellular differentiation and function. To determine the role of C/EBP transcription factors in osteoblasts and odontoblasts, we generated a transgenic (TG) mouse model with Co1a1 (pOBCol3.6) promoter-targeted expression of a FLAG-tagged dominant negative C/EBP isoform, p20C/EBPbeta (previously LIP). Two of the four transgenic lines presented with abnormalities in the developing incisors, including breakage, overgrowth, and malocclusion. Histological examination revealed that the amount of alveolar bone was reduced in TG compared to wild-type (WT) mice. By microcomputed tomography (microCT), the bone volume fraction of the mandible was reduced at the level of the first and third molars, demonstrating a severe mandibular osteopenia. The lingual dentin morphology of TG incisors differed dramatically from WT. Labial dentin (enamel side) showed normal thickness and tubular dentin structure, whereas the lingual dentin was thinner (25-30% of WT at the alveolar crest) with an amorphous globular structure characteristic of dentin dysplasia. FLAG immunostaining was seen in both lingual and labial odontoblasts, indicating that the site-specific defect was not due to a lack of labial transgene expression. Northern blot analysis demonstrated reduced osteocalcin expression in TG mandibles, while bone sialoprotein was increased, consistent with prior results in calvariae and long bones. Dental sialophosphoprotein, a marker of the odontoblast lineage whose absence causes dentin dysplasia, was modestly reduced in TG mice by Northern blot and in situ hybridization analysis. By fluorescence microscopy, pOBCol2.3-GFP, a marker of the odontoblast lineage, was expressed in both labial and lingual odontoblasts, although GFP-marked lingual odontoblasts were more flattened than WT cells. Moreover, GFP-positive processes in the lingual dentin tubules were truncated and less organized than those in WT dentin. MicroCT analysis showed reduced tissue density in the lingual dentin. These data suggest that C/EBP transcription factors may be involved in the regulation of odontoblast polarization and dentin matrix production.
Authors:
T Savage; T Bennett; Y-F Huang; P L Kelly; N E Durant; D J Adams; M Mina; J R Harrison
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Publication Detail:
Type:  Journal Article     Date:  2006-05-06
Journal Detail:
Title:  Bone     Volume:  39     ISSN:  8756-3282     ISO Abbreviation:  Bone     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-07     Completed Date:  2006-09-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8504048     Medline TA:  Bone     Country:  United States    
Other Details:
Languages:  eng     Pagination:  552-64     Citation Subset:  IM    
Affiliation:
Department of Craniofacial Sciences, Pediatric Dentistry and Advanced Education in General Dentistry, University of Connecticut Health Center, Farmington, CT 06030, USA.
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MeSH Terms
Descriptor/Qualifier:
Alveolar Bone Loss / genetics,  metabolism*,  pathology
Animals
CCAAT-Enhancer-Binding Protein-alpha / metabolism
CCAAT-Enhancer-Binding Protein-beta / genetics,  metabolism*
Dentin Dysplasia / genetics,  metabolism*,  pathology
Gene Expression
Genes, Reporter / genetics
Immunohistochemistry
Incisor / metabolism,  pathology
Mice
Mice, Transgenic
Phenotype*
Tomography, Emission-Computed
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Protein-alpha; 0/CCAAT-Enhancer-Binding Protein-beta

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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