Noggin inhibition of mouse dentinogenesis.
Bone morphogenetic protein
Dentin
Dentinogenesis imperfecta
Tooth
Transforming growth factor beta
Journal
Journal of oral biosciences
ISSN: 1880-3865
Titre abrégé: J Oral Biosci
Pays: Netherlands
ID NLM: 101226721
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
26
08
2019
revised:
18
11
2019
accepted:
20
11
2019
pubmed:
22
12
2019
medline:
18
8
2020
entrez:
22
12
2019
Statut:
ppublish
Résumé
The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore disrupt dentinogenesis by differentiated odontoblasts. We generated mice overexpressing the BMP-inhibitory protein Noggin in differentiated odontoblasts and osteocytes under control of a Dmp1 promoter-driven cre transgene. We compared the dentin phenotype in these mice with that in WT littermates and in mice with a Smad4 odontoblast/osteocyte knockout mediated by the same cre and therefore lacking all BMP and Tgfβ signaling in the same tissues. Three-month-old first molars from both Noggin-expressing and Smad4-deleted mice showed decreased dentin volume with enlarged pulp cavities, and both displayed less organized and mineralized dentinal tubules compared to WT. The Smad4-ablated phenotype was more severe. While dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) were decreased in the dentin of both lines, dentin matrix protein 1 (DMP1) was sharply increased in Noggin-expressing teeth. The phenotypes we observed in Noggin-overexpressing and Smad4-conditional knockout teeth resemble the phenotype of Dentinogenesis Imperfecta (DGI) type III. Our results show that BMPs regulate post-natal dentinogenesis and that BMP-inhibitory proteins like Noggin play a role in that regulation. The increased severity of the Smad4 phenotype indicates that Tgfβ ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.
Identifiants
pubmed: 31862386
pii: S1349-0079(19)30242-7
doi: 10.1016/j.job.2019.11.001
pmc: PMC6959969
mid: NIHMS1547183
pii:
doi:
Substances chimiques
Carrier Proteins
0
Extracellular Matrix Proteins
0
Phosphoproteins
0
Sialoglycoproteins
0
noggin protein
148294-77-3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
72-79Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE022549
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE022804
Pays : United States
Informations de copyright
Copyright © 2019 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest All of the authors declare no conflict of interest.
Références
Arch Oral Biol. 2018 Jun;90:33-39
pubmed: 29529483
J Biol Chem. 2003 Jul 4;278(27):24874-80
pubmed: 12721295
Science. 1998 Nov 6;282(5391):1136-8
pubmed: 9804553
Cells Tissues Organs. 2011;194(2-4):216-21
pubmed: 21597270
Dev Biol. 2001 Dec 15;240(2):457-73
pubmed: 11784076
Dev Dyn. 1997 Mar;208(3):349-62
pubmed: 9056639
Int J Biol Sci. 2012;8(2):272-88
pubmed: 22298955
J Bone Miner Res. 2011 Feb;26(2):229-38
pubmed: 21254230
J Cell Biochem. 1994 Jul;55(3):350-7
pubmed: 7962167
Cell. 1997 Jul 25;90(2):247-55
pubmed: 9244299
J Dent Res. 2012 Jan;91(1):58-64
pubmed: 21984706
Genesis. 2002 Feb;32(2):80-1
pubmed: 11857783
Development. 2004 Aug;131(15):3501-12
pubmed: 15215210
Dev Cell. 2004 Nov;7(5):719-30
pubmed: 15525533
Int J Dev Biol. 2006;50(6):511-21
pubmed: 16741866
Crit Rev Oral Biol Med. 1991;2(3):369-87
pubmed: 1654141
Int J Biochem Cell Biol. 2011 Apr;43(4):478-81
pubmed: 21256973
J Dent Res. 2012 Jul;91(7):690-5
pubmed: 22592126
Development. 2015 Jan 1;142(1):128-39
pubmed: 25428587
J Dent Res. 2019 Jul;98(8):912-919
pubmed: 31173534
Evol Dev. 2005 Sep-Oct;7(5):440-57
pubmed: 16174037
Bone. 2010 Jun;46(6):1533-45
pubmed: 20206312
Dev Biol. 2009 Jun 1;330(1):131-41
pubmed: 19341725
J Dent Res. 1998 Apr;77(4):545-54
pubmed: 9539457
J Exp Zool B Mol Dev Evol. 2009 Jun 15;312B(4):309-19
pubmed: 19156667
Mech Dev. 2007 Jul;124(6):409-15
pubmed: 17449229
Dev Dyn. 1997 Dec;210(4):383-96
pubmed: 9415424
Cytokine Growth Factor Rev. 2009 Oct-Dec;20(5-6):343-55
pubmed: 19897402
Cytokine Growth Factor Rev. 2005 Jun;16(3):309-17
pubmed: 15951218
Science. 2005 Sep 23;309(5743):2067-70
pubmed: 16179481
J Dent Res. 2007 Apr;86(4):320-5
pubmed: 17384025
Cell Signal. 2011 Apr;23(4):609-20
pubmed: 20959140
Matrix Biol. 2016 May-Jul;52-54:95-112
pubmed: 26686820
Genes Dis. 2014 Sep;1(1):87-105
pubmed: 25401122
Cell. 1993 Oct 8;75(1):45-58
pubmed: 8104708
Nature. 2000 Feb 10;403(6770):658-61
pubmed: 10688202
J Biol Chem. 2013 Mar 8;288(10):7204-14
pubmed: 23349460
Histochem J. 1979 Jul;11(4):447-55
pubmed: 91593