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. © international & american associations for dental research.