Unknown

Dataset Information

0

Hypophosphatasia-associated deficiencies in mineralization and gene expression in cultured dental pulp cells obtained from human teeth.


ABSTRACT: Mutations in the gene ALPL in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase, and the resulting increase in pyrophosphate (PP(i)) contributes to bone and tooth mineralization defects by inhibiting physiologic calcium-phosphate (P(i)) precipitation. Although periodontal phenotypes are well documented, pulp/dentin abnormalities have been suggested in the clinical literature although reports are variable and underlying mechanisms remains unclear. In vitro analyses were used to identify mechanisms involved in HPP-associated pulp/dentin phenotypes.Primary pulp cells cultured from HPP subjects were established to assay alkaline phosphatase (ALP) activity, mineralization, and gene expression compared with cells from healthy controls. Exogenous P(i) was provided to the correct P(i)/PP(i) ratio in cell culture.HPP cells exhibited significantly reduced ALP activity (by 50%) and mineral nodule formation (by 60%) compared with the controls. The expression of PP(i) regulatory genes was altered in HPP pulp cells, including reduction in the progressive ankylosis gene (ANKH) and increased ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Odontoblast marker gene expression was disrupted in HPP cells, including reduced osteopontin (OPN), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoprotein (MEPE). The addition of P(i) provided a corrective measure for mineralization and partially rescued the expression of some genes although cells retained altered messenger RNA levels for PP(i)-associated genes.These studies suggest that under HPP conditions pulp cells have the compromised ability to mineralize and feature a disrupted odontoblast profile, providing a first step toward understanding the molecular mechanisms for dentin phenotypes observed in HPP.

SUBMITTER: Rodrigues TL 

PROVIDER: S-EPMC3547603 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Hypophosphatasia-associated deficiencies in mineralization and gene expression in cultured dental pulp cells obtained from human teeth.

Rodrigues Thaisângela L TL   Foster Brian L BL   Silverio Karina G KG   Martins Luciane L   Casati Marcio Z MZ   Sallum Enilson A EA   Somerman Martha J MJ   Nociti Francisco H FH  

Journal of endodontics 20120329 7


<h4>Introduction</h4>Mutations in the gene ALPL in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase, and the resulting increase in pyrophosphate (PP(i)) contributes to bone and tooth mineralization defects by inhibiting physiologic calcium-phosphate (P(i)) precipitation. Although periodontal phenotypes are well documented, pulp/dentin abnormalities have been suggested in the clinical literature although reports are variable and underlying mechanisms remains u  ...[more]

Similar Datasets

| S-EPMC5408163 | biostudies-literature
2014-08-21 | GSE51449 | GEO
2014-08-21 | E-GEOD-51449 | biostudies-arrayexpress
| S-EPMC3871996 | biostudies-literature
| S-EPMC6429567 | biostudies-literature
| S-EPMC8829122 | biostudies-literature
| S-EPMC6901003 | biostudies-literature
2016-11-22 | GSE50639 | GEO
2022-06-01 | GSE193471 | GEO
| S-EPMC6646701 | biostudies-literature