Circ-AARS plays an important role during the odontogenic differentiation of dental pulp stem cells by modulating miR-24-3p/KLF6 expression.

IF 7.1 2区 医学 Q1 CELL & TISSUE ENGINEERING Stem Cell Research & Therapy Pub Date : 2025-03-13 DOI:10.1186/s13287-025-04239-z
Meizhi Sui, Jiaxuan Lyu, Jiaxin Zhou, Qian Liao, Zexu Xiao, Mingming Jin, Jiang Tao
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Abstract

Background: Circular 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.

Methods: In 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.

Results: High-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.

Conclusion: The 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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Stem Cell Research & Therapy
Stem Cell Research & Therapy CELL BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
13.20
自引率
8.00%
发文量
525
审稿时长
1 months
期刊介绍: Stem Cell Research & Therapy serves as a leading platform for translational research in stem cell therapies. This international, peer-reviewed journal publishes high-quality open-access research articles, with a focus on basic, translational, and clinical research in stem cell therapeutics and regenerative therapies. Coverage includes animal models and clinical trials. Additionally, the journal offers reviews, viewpoints, commentaries, and reports.
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