PMID- 29489425
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20190624
IS  - 1544-0591 (Electronic)
IS  - 0022-0345 (Linking)
VI  - 97
IP  - 7
DP  - 2018 Jul
TI  - Bone Morphogenetic Protein 2 Coordinates Early Tooth Mineralization.
PG  - 835-843
LID - 10.1177/0022034518758044 [doi]
AB  - Formation of highly organized dental hard tissues is a complex process involving 
      sequential and ordered deposition of an extracellular scaffold, followed by its 
      mineralization. Odontoblast and ameloblast differentiation involves reciprocal 
      and sequential epithelial-mesenchymal interactions. Similar to early tooth 
      development, various Bmps are expressed during this process, although their 
      functions have not been explored in detail. Here, we investigated the role of 
      odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout 
      mice. In developing molars, Bmp2LacZ reporter mice revealed restricted expression 
      of Bmp2 in early polarized and functional odontoblasts while it was not expressed 
      in mature odontoblasts. Loss of Bmp2 in neural crest cells, which includes all 
      dental mesenchyme, caused a delay in dentin and enamel deposition. 
      Immunohistochemistry for nestin and dentin sialoprotein (Dsp) revealed 
      polarization defects in odontoblasts, indicative of a role for Bmp2 in 
      odontoblast organization. Surprisingly, pSmad1/5/8, an indicator of Bmp 
      signaling, was predominantly reduced in ameloblasts, with reduced expression of 
      amelogenin ( Amlx), ameloblastin ( Ambn), and matrix metalloproteinase ( Mmp20). 
      Quantitative real-time polymerase chain reaction (RT-qPCR) analysis and 
      immunohistochemistry showed that loss of Bmp2 resulted in increased expression of 
      the Wnt antagonists dickkopf 1 ( Dkk1) in the epithelium and sclerostin ( Sost) 
      in mesenchyme and epithelium. Odontoblasts showed reduced Wnt signaling, which is 
      important for odontoblast differentiation, and a strong reduction in dentin 
      sialophosphoprotein ( Dspp) but not collagen 1 a1 ( Col1a1) expression. Mature 
      Bmp2-deficient teeth, which were obtained by transplanting tooth germs from 
      Bmp2-deficient embryos under a kidney capsule, showed a dentinogenesis imperfecta 
      type II-like appearance. Micro-computed tomography and scanning electron 
      microscopy revealed reduced dentin and enamel thickness, indistinguishable 
      primary and secondary dentin, and deposition of ectopic osteodentin. This 
      establishes that Bmp2 provides an early temporal, nonredundant signal for 
      directed and organized tooth mineralization.
FAU - Malik, Z
AU  - Malik Z
AD  - 1 School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, 
      Edmonton, AB, Canada.
FAU - Alexiou, M
AU  - Alexiou M
AD  - 1 School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, 
      Edmonton, AB, Canada.
FAU - Hallgrimsson, B
AU  - Hallgrimsson B
AD  - 2 Department of Cell Biology and Anatomy, Faculty of Medicine, University of 
      Calgary, AB, Canada.
FAU - Economides, A N
AU  - Economides AN
AD  - 3 Regeneron Pharmaceuticals, Tarrytown, NY, USA.
FAU - Luder, H U
AU  - Luder HU
AD  - 4 Institute of Oral Biology, Centre for Dental Medicine, Faculty of Medicine, 
      University of Zurich, Zurich, Switzerland.
FAU - Graf, D
AU  - Graf D
AUID- ORCID: 0000-0003-1163-8117
AD  - 1 School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, 
      Edmonton, AB, Canada.
AD  - 5 Department of Medical Genetics, Faculty of Medicine and Dentistry, University 
      of Alberta, Edmonton, AB, Canada.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180228
PL  - United States
TA  - J Dent Res
JT  - Journal of dental research
JID - 0354343
RN  - 0 (Ambn protein, mouse)
RN  - 0 (Amelogenin)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Dental Enamel Proteins)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Nestin)
RN  - 0 (Phosphoproteins)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Smad Proteins)
RN  - 0 (dentin sialophosphoprotein)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 20)
RN  - EC 3.4.24.- (Mmp20 protein, mouse)
SB  - IM
MH  - Amelogenin/metabolism
MH  - Animals
MH  - Bone Morphogenetic Protein 2/*metabolism
MH  - Dental Enamel Proteins/metabolism
MH  - Dentinogenesis Imperfecta/metabolism/physiopathology
MH  - Extracellular Matrix Proteins/metabolism
MH  - Immunohistochemistry
MH  - Matrix Metalloproteinase 20/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Electron, Scanning
MH  - Molar/metabolism
MH  - Nestin/metabolism
MH  - Odontoblasts/*metabolism
MH  - Phosphoproteins/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Sialoglycoproteins/metabolism
MH  - Signal Transduction
MH  - Smad Proteins/metabolism
MH  - Tooth Calcification/*physiology
MH  - X-Ray Microtomography
OTO - NOTNLM
OT  - dentin
OT  - epithelial-mesenchymal interaction
OT  - gene expression
OT  - mouse genetics
OT  - osteodentin
OT  - signaling
EDAT- 2018/03/01 06:00
MHDA- 2019/06/25 06:00
CRDT- 2018/03/01 06:00
PHST- 2018/03/01 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2018/03/01 06:00 [entrez]
AID - 10.1177/0022034518758044 [doi]
PST - ppublish
SO  - J Dent Res. 2018 Jul;97(7):835-843. doi: 10.1177/0022034518758044. Epub 2018 Feb 
      28.