Hsa‐miR‐27b‐5p suppresses the osteogenic and odontogenic differentiation of stem cells from human exfoliated deciduous teeth via targeting BMPR1A: An ex vivo study

Abstract

AbstractAimRecently, miR‐27b‐5p was shown to be abundantly expressed in extracellular vehicles (EVs) from the inflammatory microenvironment. This study determined the role of miR‐27b‐5p in regulating osteogenic and odontogenic differentiation of stem cells from human exfoliated deciduous teeth (SHEDs) and further examined the regulatory mechanism of bone morphogenetic protein receptor type‐1A (BMPR1A).MethodologyCharacteristics of SHEDs and SHEDs‐EVs derived from SHEDs were evaluated respectively. The expression of miR‐27b‐5p in SHEDs and EVs was detected during osteo‐induction. Mechanically, SHEDs were treated with miR‐27b‐5p mimics or an inhibitor, and the osteogenic/odontogenic differentiation and proliferation were assessed. Bioinformatic analysis and luciferase reporter were utilized for target gene prediction and verification. Finally, BMPR1A‐overexpressed plasmids were transfected into SHEDs to investigate the participation of the BMPR1A/SMAD4 pathway. Data were analysed using Student's t‐test, one‐way analysis of variance and Chi‐square test.ResultsMiR‐27b‐5p was expressed in both SHEDs and EVs and was significantly increased at the initial stage of differentiation and then decreased in a time‐dependent manner (p < .01). Upregulation of miR‐27b‐5p significantly suppressed osteogenic/odontogenic differentiation of SHEDs and inhibited proliferation (p < .05), whereas inhibition of miR‐27b‐5p enhanced the differentiation (p < .05). Dual‐luciferase reporter assay and pull‐down assay confirmed the binding site between miR‐27b‐5p and BMPR1A (p < .05). The overexpression of BMPR1A rescued the effect of miR‐27b‐5p, while contributed to the decrease of pluripotency (p < .05). Additionally, miR‐27b‐5p maintained pluripotency in BMPR1A‐overexpressed SHEDs (p < .05).ConclusionsMiR‐27b‐5p in SHEDs/EVs was inversely associated with differentiation and suppressed the osteogenic and odontogenic differentiation of SHEDs and maintained the pluripotency of SHEDs partly by shuttering BMPR1A‐targeting BMP signalling. Theoretically, inhibition of miR‐27b‐5p represents a potential strategy to promote osteanagenesis and dentinogenesis. However, miR‐27b‐5p capsuled EVs might maintain cell pluripotency and self‐renewal for non‐cell‐targeted therapy.