Involvement of miR‐146a‐5p/neurogenic locus notch homolog protein 1 in the proliferation and differentiation of STRO‐1⁺ human dental pulp stem cells

Abstract

Dental pulp stem cells (DPSCs) and stem cells from the apical papilla (SCAPs) are oral mesenchymal stem cells capable of self‐renewal and have a potential for multilineage differentiation. Increasing evidence shows that microRNAs (miRNAs) play important roles in stem cell biology. Here, we focused on exploring miR‐146a‐5p and its relationship to the undifferentiated status of STRO‐1 + SCAPs and STRO‐1 + DPSCs, as well as its role during STRO‐1 + DPSC differentiation and proliferation. Our data indicated that baseline miR‐146a‐5p expression is significantly lower in STRO‐1 + SCAPs than in STRO‐1 + DPSCs and increased in the latter during osteogenic induction. Moreover, we identified miR‐146a‐5p as a key miRNA that promotes osteo/odontogenic differentiation of STRO‐1 + DPSCs and attenuates cell proliferation. Additionally, it was observed that STRO‐1 + DPSC mineralization results in the downregulation of notch receptor 1 ( NOTCH1 ) and hes family bHLH transcription factor 1 ( HES1 ). Interference with neurogenic locus notch homolog protein 1 (Notch 1) signaling was verified to enhance differentiation and suppress STRO‐1 + DPSC proliferation. It was further observed that miR‐146a‐5p directly targets the 3′‐untranslated region (3′‐UTR) of NOTCH1 and inhibits expression of both NOTCH1 and HES1 mRNAs and Notch 1 and transcription factor HES‐1 (HES‐1) proteins in STRO‐1 + DPSCs. We conclude that miR‐146a‐5p exerts its regulatory effect on STRO‐1 + DPSC differentiation and proliferation partially by suppressing Notch signaling.