Klf5 Mediates Odontoblastic Differentiation through Regulating Dentin-Specific Extracellular Matrix Gene Expression during Mouse Tooth Development

Abstract

Klf5, a member of the Krüppel-like transcription factor family, has essential roles during embryonic development, cell proliferation, differentiation, migration and apoptosis. This study was to define molecular mechanism of Klf5 during the odontoblastic differentiation. The expression of Klf5, odontoblast-differentiation markers, Dspp and Dmp1 was co-localized in odontoblastic cells at different stages of mouse tooth development and mouse dental papilla mesenchymal cells. Klf5 was able to promote odontoblastic differentiation and enhance mineral formation of mouse dental papilla mesenchymal cells. Furthermore, overexpression of Klf5 could up-regulate Dspp and Dmp1 gene expressions in mouse dental papilla mesenchymal cells. In silico analysis identified that several putative Klf5 binding sites in the promoter and first intron of Dmp1 and Dspp genes that are homologous across species lines. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis indicated that Klf5 bound to these motifs in vitro and in intact cells. The responsible regions of Dmp1 gene were located in the promoter region while effect of Klf5 on Dspp activity was in the first intron of Dspp gene. Our results identify Klf5 as an activator of Dmp1 and Dspp gene transcriptions by different mechanisms and demonstrate that Klf5 plays a pivotal role in odontoblast differentiation.

Evaluation of odonto/osteogenic differentiation potential from different regions derived dental tissue stem cells and effect of 17β-estradiol on efficiency

“…It has been demonstrated that the dentin is composed of mineral substance and odontoblasts formed these mineral matrix and deposited calcium [ 28 ]. All odonto/osteoblasts from dental MSCs were positively stained with ALP and Von kossa.…”

“…Furthermore, the odonto/osteoblasts from DPSCs were most strongly stained with both. Several studies have mentioned the ALP activity as an early marker of odontoblast differentiation [ 11 , 28 ]. In our study, the expression of ALP activity was significantly higher expressed in odonto/osteoblasts when compared to undifferentiated dental MSCs.…”

“…The possible reason behind these results could be due to the different origins and their varied response under used in vitro induction conditions. Recent studies revealed that odontoblasts and osteoblasts share similar origin and both cells had the capacity of mineral formation and calcium deposition [ 28 ]. Furthermore, it has also been demonstrated that DMP-1 and DSPP are highly expressed in odontoblasts than osteoblasts and ALP, which is also primary marker of osteoblasts showed different expression pattern with DMP-1 and DSPP [ 32 ].…”

MiR-143-3p Inhibits Osteogenic Differentiation of Human Periodontal Ligament Cells by Targeting KLF5 and Inactivating the Wnt/β-Catenin Pathway

“…The results revealed that the levels of OCN, OPN, ALP, and Runx2 were promoted from the 7th to the 21st day (all p < 0.05; Figures 1F , G , H ). KLF5 is differentially expressed during tooth development, and may play a vital role during in the osteogenesis of hPDLCs ( Chen et al, 2009 , 2017 ; Mihara et al, 2017 ). We exhibited that KLF5 expression was enhanced notably at the 7th, 14th, and 21st day after osteogenesis induction (all p < 0.05; Figures 1I , J ).…”

“…KLF5 participates in the cell proliferation during tooth development and also relates to the mineralization of enamel and dentin matrix ( Chen et al, 2009 ). KLF5 can enhance the differentiation of odontoblasts and promote the mineral formation of dental papilla mesenchymal cells in a mouse model ( Chen et al, 2017 ). At present, the function of KLF5 in the osteogenesis of hPDLCs is still an intriguing issue waiting to be explored.…”