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Quaking promotes the odontoblastic differentiation of human dental pulp stem cells
Author(s) -
Li Shuchen,
Lin Chujiao,
Zhang Jie,
Tao Huangheng,
Liu Huan,
Yuan Guohua,
Chen Zhi
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26561
Subject(s) - klf4 , dental pulp stem cells , microbiology and biotechnology , gene knockdown , competing endogenous rna , transcription factor , dentinogenesis , dentin sialophosphoprotein , sox2 , odontoblast , cellular differentiation , microrna , stem cell , chemistry , rna , biology , pulp (tooth) , gene , long non coding rna , pathology , biochemistry , medicine
Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) is essential for the formation of reparative dentin after dental caries or injury. Our previous studies have demonstrated that krüppel‐like factor 4 (KLF4) is a critical transcription factor that promotes the odontoblastic differentiation of hDPSCs. Analysis of the microRNA binding sites within the 3′‐UTR of KLF4 revealed that QKI , an RNA‐binding protein, shared the most microRNAs with KLF4 , presumably served as a “competent endogenous RNA (ceRNA)” with KLF4 . Thus, we hypothesized QKI could also promote odontoblastic differentiation. In this study, we found QKI was up‐regulated during mouse odontoblast differentiation in vivo and hDPSCs odontoblastic differentiation in vitro. Overexpression or knockdown of QKI in hDPSCs led to the increase or decrease of odontoblast marker genes’ expressions, indicating its positive role in odontoblastic differentiation. We further validated that QKI served as a key ceRNA of KLF4 via interaction of the shared miRNAs in hDPSCs. Last, we found that, as an RNA binding protein, QKI protein could bind to, and stabilize dentin sialophosphoprotein ( DSPP ) mRNA, resulting in the augmented accumulation of DSP protein. Taken together, our study indicates that QKI promotes the odontoblastic differentiation of hDPSCs by acting as a ceRNA of KLF4 and as a binding protein of DSPP mRNA to stabilize its level. These two mechanisms of QKI will together positively regulate the downstream pathways and hence potentiate odontoblastic differentiation.