COUP-TFII Stimulates Dentin Sialophosphoprotein Expression and Mineralization in Odontoblasts.
Chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII), an orphan nuclear receptor belonging to the steroid-thyroid hormone receptor superfamily, plays an important role in cell fate determination of various tissues. However, the specific role of COUP-TFII in tooth development has not yet been elucidated. In the present study, we aimed to explore the role of COUP-TFII in dentin sialophosphoprotein (DSPP) expression and matrix mineralization in odontoblast-lineage cells. In primary human dental pulp cells (HDPCs) and murine dental papilla-derived cells (MDPC-23) cultured in a mineralizing medium, the expression of COUP-TFII was induced along with the increased odontoblast-specific dentin matrix protein-1 (DMP-1) and DSPP expression. Endogenous expression of COUP-TFII in maxillary second molar germs of rats showed an increasing tendency as development of the tooth progressed. Also, COUP-TFII protein was detected in greater quantity in the odontoblastic layer of second molar germs than in that of third molar germs of rats. Overexpression of COUP-TFII using an adenoviral system upregulated the expression of odontoblast-specific genes with increased alkaline phosphatase activity and matrix mineralization in odontoblast-lineage cells. In contrast, knockdown of COUP-TFII using small interfering RNA decreased the expression of odontoblast-specific genes, which reduced matrix mineralization. Mechanistic studies revealed that COUP-TFII increased DSPP transcription by direct binding on the DSPP promoter. In addition, COUP-TFII physically interacted with the homeodomain transcription factor Msx2 and antagonistically regulated the Msx2 effect on DSPP promoter activity. Taken together, these results suggest that COUP-TFII has a stimulatory role in DSPP expression and matrix mineralization in odontoblast-lineage cells.
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea.
S-W
SW
Hur
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea.
S-H
SH
Oh
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea.
B-C
BC
Jeong
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea.
H
H
Choi
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea.
J-W
JW
Kim
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea.
K-N
KN
Lee
Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea Department of Conservative Dentistry, School of Dentistry, Chonnam National University, Gwangju, South Korea.
Y-C
YC
Hwang
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea.
J-H
JH
Ryu
Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea.
S-H
SH
Kim
Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, South Korea Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, South Korea jtkoh@chonnam.ac.kr.
J-T
JT
Koh
D000818:Animals; D015153:Blotting, Western; D051837:COUP Transcription Factor II / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003810:Dentinogenesis; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D009804:Odontoblasts / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000378:metabolism*; D013194:Staining and Labeling; D014162:Transfection; D000099311:Dentin Sialophosphoprotein
D051837:COUP Transcription Factor II; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D010750:Phosphoproteins; D012795:Sialoglycoproteins; D000099311:Dentin Sialophosphoprotein; C084119:MSX2 protein
DSPP; Msx2; dental pulp; orphan nuclear receptor; tooth germ; transcription factor