Cargando…

DSPP dosage affects tooth development and dentin mineralization

Dentin Sialoprotein (DSP) and phosphophoryn (PP) are two most dominant non-collagenous proteins in dentin, which are the cleavage products of the DSPP (dentin sialophosphoprotein) precursor protein. The absence of the DSPP gene in DSPP knock-out (KO) mice results in characteristics that are consiste...

Descripción completa

Detalles Bibliográficos
Autores principales: Lim, Dandrich, Wu, Ko-Chien, Lee, Arthur, Saunders, Thomas L., Ritchie, Helena H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153449/
https://www.ncbi.nlm.nih.gov/pubmed/34038418
http://dx.doi.org/10.1371/journal.pone.0250429
_version_ 1783698800800432128
author Lim, Dandrich
Wu, Ko-Chien
Lee, Arthur
Saunders, Thomas L.
Ritchie, Helena H.
author_facet Lim, Dandrich
Wu, Ko-Chien
Lee, Arthur
Saunders, Thomas L.
Ritchie, Helena H.
author_sort Lim, Dandrich
collection PubMed
description Dentin Sialoprotein (DSP) and phosphophoryn (PP) are two most dominant non-collagenous proteins in dentin, which are the cleavage products of the DSPP (dentin sialophosphoprotein) precursor protein. The absence of the DSPP gene in DSPP knock-out (KO) mice results in characteristics that are consistent with dentinogenesis imperfecta type III in humans. Symptoms include thin dentin, bigger pulp chamber with frequent pulp exposure as well as abnormal epithelial-mesenchymal interactions, and the appearance of chondrocyte-like cells in dental pulp. To better understand how DSPP influences tooth development and dentin formation, we used a bacterial artificial chromosome transgene construct (BAC-DSPP) that contained the complete DSPP gene and promoter to generate BAC-DSPP transgenic mice directly in a mouse DSPP KO background. Two BAC-DSPP transgenic mouse strains were generated and characterized. DSPP mRNA expression in BAC-DSPP Strain A incisors was similar to that from wild-type (wt) mice. DSPP mRNA expression in BAC-DSPP Strain B animals was only 10% that of wt mice. PP protein content in Strain A incisors was 25% of that found in wt mice, which was sufficient to completely rescue the DSPP KO defect in mineral density, since microCT dentin mineral density analysis in 21-day postnatal animal molars showed essentially identical mineral density in both strain A and wt mice. Strain B mouse incisors, with 5% PP expression, only partially rescued the DSPP KO defect in mineral density, as microCT scans of 21-day postnatal animal molars indicated a reduced dentin mineral density compared to wt mice, though the mineral density was still increased over that of DSPP KO. Furthermore, our findings showed that DSPP dosage in Strain A was sufficient to rescue the DSPP KO defect in terms of epithelial-mesenchymal interactions, odontoblast lineage maintenance, along with normal dentin thickness and normal mineral density while DSPP gene dosage in Strain B only partially rescued the aforementioned DSPP KO defect.
format Online
Article
Text
id pubmed-8153449
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-81534492021-06-07 DSPP dosage affects tooth development and dentin mineralization Lim, Dandrich Wu, Ko-Chien Lee, Arthur Saunders, Thomas L. Ritchie, Helena H. PLoS One Research Article Dentin Sialoprotein (DSP) and phosphophoryn (PP) are two most dominant non-collagenous proteins in dentin, which are the cleavage products of the DSPP (dentin sialophosphoprotein) precursor protein. The absence of the DSPP gene in DSPP knock-out (KO) mice results in characteristics that are consistent with dentinogenesis imperfecta type III in humans. Symptoms include thin dentin, bigger pulp chamber with frequent pulp exposure as well as abnormal epithelial-mesenchymal interactions, and the appearance of chondrocyte-like cells in dental pulp. To better understand how DSPP influences tooth development and dentin formation, we used a bacterial artificial chromosome transgene construct (BAC-DSPP) that contained the complete DSPP gene and promoter to generate BAC-DSPP transgenic mice directly in a mouse DSPP KO background. Two BAC-DSPP transgenic mouse strains were generated and characterized. DSPP mRNA expression in BAC-DSPP Strain A incisors was similar to that from wild-type (wt) mice. DSPP mRNA expression in BAC-DSPP Strain B animals was only 10% that of wt mice. PP protein content in Strain A incisors was 25% of that found in wt mice, which was sufficient to completely rescue the DSPP KO defect in mineral density, since microCT dentin mineral density analysis in 21-day postnatal animal molars showed essentially identical mineral density in both strain A and wt mice. Strain B mouse incisors, with 5% PP expression, only partially rescued the DSPP KO defect in mineral density, as microCT scans of 21-day postnatal animal molars indicated a reduced dentin mineral density compared to wt mice, though the mineral density was still increased over that of DSPP KO. Furthermore, our findings showed that DSPP dosage in Strain A was sufficient to rescue the DSPP KO defect in terms of epithelial-mesenchymal interactions, odontoblast lineage maintenance, along with normal dentin thickness and normal mineral density while DSPP gene dosage in Strain B only partially rescued the aforementioned DSPP KO defect. Public Library of Science 2021-05-26 /pmc/articles/PMC8153449/ /pubmed/34038418 http://dx.doi.org/10.1371/journal.pone.0250429 Text en © 2021 Lim et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lim, Dandrich
Wu, Ko-Chien
Lee, Arthur
Saunders, Thomas L.
Ritchie, Helena H.
DSPP dosage affects tooth development and dentin mineralization
title DSPP dosage affects tooth development and dentin mineralization
title_full DSPP dosage affects tooth development and dentin mineralization
title_fullStr DSPP dosage affects tooth development and dentin mineralization
title_full_unstemmed DSPP dosage affects tooth development and dentin mineralization
title_short DSPP dosage affects tooth development and dentin mineralization
title_sort dspp dosage affects tooth development and dentin mineralization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153449/
https://www.ncbi.nlm.nih.gov/pubmed/34038418
http://dx.doi.org/10.1371/journal.pone.0250429
work_keys_str_mv AT limdandrich dsppdosageaffectstoothdevelopmentanddentinmineralization
AT wukochien dsppdosageaffectstoothdevelopmentanddentinmineralization
AT leearthur dsppdosageaffectstoothdevelopmentanddentinmineralization
AT saundersthomasl dsppdosageaffectstoothdevelopmentanddentinmineralization
AT ritchiehelenah dsppdosageaffectstoothdevelopmentanddentinmineralization