miR-140-5p-mediated regulation of the proliferation and differentiation of human dental pulp stem cells occurs through the lipopolysaccharide/toll-like receptor 4 signaling pathway

Human dental pulp stem cells (DPSCs) are oral mesenchymal stem cells with potential to differentiate into various cell types. Recent studies of DPSCs have focused on microRNAs (miRNAs), a class of small noncoding RNAs that play crucial roles in regulating DPSC phenotypes. In the current study, the expression of miR-140-5p was significantly decreased during lipopolysaccharide (LPS)-mediated differentiation of DPSCs in vitro. Overexpression of miR-140-5p enhanced proliferation of DPSCs and inhibited DPSC differentiation, whereas suppression of miR-140-5p produced the opposite effect. Moreover, the expression of toll-like receptor 4 (TLR-4), a critical regulator of DPSCs, was negatively correlated with the levels of miR-140-5p. A luciferase reporter analysis confirmed that miR-140-5p could regulate TLR-4 by directly binding to the 3′-untranslated region (3′-UTR) of the TLR4 mRNA. Additionally, we suppressed TLR-4 expression by treating cells with a TLR-4 inhibitor, CLI-095, and demonstrated that the effect of the miR-140-5p inhibitor on DPSC proliferation and differentiation could be partially reversed by blocking TLR-4. Taken together, our data suggest that miR-140-5p is a novel miRNA that regulates DPSC proliferation and differentiation.

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