LAUSR

ABSTRACT In a previous study, we showed that microRNA‐675 (miR‐675) was significantly down‐regulated in patients with tricho‐dento‐osseous (TDO) syndrome. One of the main features of TDO syndrome is dentin hypoplasia. Thus, we hypothesize that miR‐675 plays a role in dentin development. In this study, we determined the role of miR‐675 in the odontogenic differentiation of human dental pulp cells (hDPCs). Stable overexpression and knockdown of miR‐675 in hDPCs were performed using recombinant lentiviruses containing U6 promoter‐driven miR‐675 and short hairpin‐miR675 expression cassettes, respectively. Alkaline phosphatase (ALP) assay, Alizarin red staining assay, quantitative polymerase chain reaction (qPCR), Western blot analysis, and immunofluorescent staining revealed the promotive effects of miR‐675 on the odontogenic differentiation of hDPCs. Further, we found that miR‐675 facilitates the odontogenic differentiation process of hDPCs by epigenetic regulation of distal‐less homeobox (DLX3). Thus, for the first time, we determined that miR‐675 regulates the odontogenic differentiation of hDPCs by inhibiting the DNA methyltransferase 3 beta (DNMT3B)‐mediated methylation of DLX3. Our findings uncover an unanticipated regulatory role for miR‐675 in the odontogenic differentiation of hDPCs by epigenetic changes in DLX3 and provide novel insight into dentin hypoplasia feature in TDO patients. HIGHLIGHTSmiR‐675 promotes the odontogenic differentiation of human dental pulp cells (hDPCs).miR‐675 regulates the odontogenic differentiation of hDPCs by epigenetic regulating DLX3.Our findings shed light on the regulatory mechanism of dentin hypoplasia in TDO patients.