Dysregulated circARF3/miR-27b-3p/YAP1 contributes to impaired osteogenic differentiation of periodontal ligament stem cells in periodontitis

doi:10.4252/wjsc.116004

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World Journal of Stem Cells

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1948-0210

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Stem Cells. Jun 26, 2026; 18(6): 116004
Published online Jun 26, 2026. doi: 10.4252/wjsc.116004

Dysregulated circARF3/miR-27b-3p/YAP1 contributes to impaired osteogenic differentiation of periodontal ligament stem cells in periodontitis

Lin Qi, Xiao-Qing Wang, Jia Sun, Rui-Zhi Li, Ze-Bin Mao

Lin Qi, Ze-Bin Mao, Department of Biochemistry and Biophysics, School of Basic Medical Sciences Peking University, Beijing 100191, China

Xiao-Qing Wang, Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Shenyang 110001, Liaoning Province, China

Jia Sun, Department of Orthodontics, Institute for Clinical Research and Application of Sunny Dental, Beijing 100022, China

Rui-Zhi Li, Department of Orthodontics, Beijing Jiuwen Dental Clinic, Beijing 102218, China

Author contributions: Qi L, Wang XQ, and Mao ZB designed and coordinated the study; Qi L, Wang XQ, Sun J, and Li RZ performed the experiments, acquired and analyzed data; Qi L, Wang XQ, Sun J, and Li RZ interpreted the data; Qi L and Mao ZB wrote the manuscript; all authors approved the final version of the article.

Institutional review board statement: This study was approved by the Ethics Committee of China Medical University (No. 2024PS237K).

Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.

Data sharing statement: No additional data are available.

Corresponding author: Ze-Bin Mao, Department of Biochemistry and Biophysics, School of Basic Medical Sciences Peking University, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China. zbmao@bjmu.edu.cn

Received: November 25, 2025
Revised: January 7, 2026
Accepted: March 17, 2026
Published online: June 26, 2026
Processing time: 211 Days and 23.8 Hours

Abstract

BACKGROUND

Periodontitis is a prevalent chronic inflammatory disease whose progression can lead to the disrupted periodontal structures and subsequent tooth loss, severely impacting patients’ lives. Hence, exploring effective treatments for periodontitis is crucial. Periodontal ligament stem cells (PDLSCs) show promise for regenerating periodontal and alveolar bone tissues. Understanding the molecular mechanisms that control the osteogenic differentiation of PDLSCs is essential for developing regenerative therapies for periodontitis. Circular RNAs (circRNAs) are a novel type of noncoding RNA that form closed loops and are more stable than linear RNAs. Nevertheless, the relationship between circRNAs, periodontitis, and the osteogenic differentiation of PDLSCs has not been extensively studied.

AIM

To explore the roles of circRNA ADP-ribosylation factor 3 (circARF3) in the osteogenic differentiation of PDLSCs and periodontitis.

METHODS

Quantitative real-time polymerase chain reaction was utilized to compare RNA expression in periodontal ligament tissues from periodontitis patients and healthy individuals. PDLSCs were isolated, and flow cytometry was used to identify their surface markers. Alizarin red staining and alkaline phosphatase staining were performed to assess PDLSC osteogenic differentiation. Western blotting was employed to measure the expression of proteins related to osteogenic differentiation, including Runx2, Osterix, Osteocalcin, and Col1a1. The ENCORI website was applied to predict the interaction between miR-27b-3p and circARF3 and the 3’ untranslated region of Yes associated protein 1 (YAP1), and this interaction was validated using luciferase reporter gene assays, RNA immunoprecipitation, and RNA pulldown.

RESULTS

circARF3 expression was decreased in periodontal ligament tissues of patients with periodontitis compared with healthy individuals (P < 0.01). circARF3 knockdown resulted in decreased alkaline phosphatase activity, alizarin red staining, and osteogenic gene expression (P < 0.01). miR-27b-3p directly binds to circARF3 and the 3’ untranslated region of YAP1. Overexpression of miR-27b-3p mimicked, and depletion of YAP1 reversed, the effect of circARF3 on PDLSC osteogenic differentiation (P < 0.01).

CONCLUSION

Depletion of circARF3 suppresses PDLSC osteogenic differentiation in periodontitis via the miR-27b-3p/YAP1 axis.

Keywords: Periodontitis; Periodontal ligament stem cells; Osteogenic differentiation; Circular RNA; MicroRNAs; Yes associated protein 1

Core Tip: Periodontal ligament stem cells are promising candidate for the regenerative treatment of periodontal and alveolar bone tissues. Circular RNA ADP-ribosylation factor 3 was decreased in the periodontal ligament tissues of periodontitis patients. Circular RNA ADP-ribosylation factor 3 promotes the osteogenic differentiation of periodontal ligament stem cells in periodontitis by acting as a sponge for miR-27b-3p and increasing the expression of its target gene, Yes associated protein 1. This suggests it could be a potential therapeutic target for regenerative treatment of periodontitis.