ArticleStem cell research & therapy2025
Circ-AARS plays an important role during the odontogenic differentiation of dental pulp stem cells by modulating miR-24-3p/KLF6 expression.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCircular RNAs (circRNAs) play a crucial role in stem cell-based tooth regeneration. However, the functions and underlying mechanisms of circRNAs in tooth regeneration from human dental pulp stem cells (DPSCs) remain largely unclear.
methodsIn this study, DPSCs were used for odontogenic differentiation. High-throughput sequencing was performed for differential circRNA analysis. A luciferase reporter assay was conducted to confirm the downstream target of the circRNA, circ-AARS. We then constructed vectors and siRNAs for overexpressing and silencing circ-AARS, miR-24-3p, and Krüppel-like factor 6 (KLF6) and transfected them into DPSCs. Alkaline phosphatase staining, Alizarin Red S staining, western blotting assay, and quantitative reverse transcription-polymerase chain reaction were used to explore the underlying mechanisms of circ-AARS. Finally, a heterotopic bone model was utilized to reveal the regulating effects of circ-AARS.
resultsHigh-throughput sequencing analysis showed that circ-AARS plays an important role during the odontogenic differentiation of DPSCs. Downregulation of circ-AARS inhibited the odontogenic differentiation of DPSCs; however, circ-AARS overexpression promoted their odontogenic differentiation. Bioinformatics analysis and luciferase reporter assay confirmed that both miR-24-3p and KLF6 were the downstream targets of circ-AARS. miR-24-3p downregulation or KLF6 overexpression restored the odontogenic differentiation ability of DPSCs after circ-AARS silencing. KLF6 upregulation restored the odontogenic differentiation ability of DPSCs after KLF6 overexpression. The heterotopic bone model confirmed that circ-AARS overexpression promoted the odontoblastic differentiation of DPSCs.
conclusionThe present study showed that circ-AARS can promote the odontoblastic differentiation of DPSCs by increasing KLF6 expression and sponging miR-24-3p. Taken together, the results indicate that circ-AARS may be a potential positive regulator of odontoblastic differentiation of DPSCs.
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