Zhao YC, Li GY, Chen S, Wang YL, Feng JY, Cao Y. Epiregulin enhances periodontal tissue regeneration by promoting bone marrow mesenchymal stem cell functions under inflammatory niches. World J Stem Cells 2026; 18(2): 114032 [DOI: 10.4252/wjsc.v18.i2.114032]
Corresponding Author of This Article
Yu Cao, PhD, Professor, Department of Wangfujing General School of Stomatology, Capital Medical University School of Stomatology, No. 11 Pewter Lane, Dongcheng District, Beijing 100010, China. caoyu_bj@163.com
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Cell & Tissue Engineering
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Basic Study
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Feb 26, 2026 (publication date) through Feb 17, 2026
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World Journal of Stem Cells
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1948-0210
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Zhao YC, Li GY, Chen S, Wang YL, Feng JY, Cao Y. Epiregulin enhances periodontal tissue regeneration by promoting bone marrow mesenchymal stem cell functions under inflammatory niches. World J Stem Cells 2026; 18(2): 114032 [DOI: 10.4252/wjsc.v18.i2.114032]
World J Stem Cells. Feb 26, 2026; 18(2): 114032 Published online Feb 26, 2026. doi: 10.4252/wjsc.v18.i2.114032
Epiregulin enhances periodontal tissue regeneration by promoting bone marrow mesenchymal stem cell functions under inflammatory niches
Ying-Chu Zhao, Guo-Yue Li, Si Chen, Yi-Lin Wang, Jing-Yi Feng, Yu Cao
Ying-Chu Zhao, Yi-Lin Wang, Jing-Yi Feng, Beijing Stomatological Hospital, Capital Medical University, Beijing 100070, China
Guo-Yue Li, Department of Emergent Dental Care and General Dentistry, Beijing Stomatological Hospital, Capital Medical University, Beijing 100070, China
Si Chen, Department of Stomatology, Beijing Youan Hospital, Beijing 100069, China
Yu Cao, Department of Wangfujing General School of Stomatology, Capital Medical University School of Stomatology, Beijing 100010, China
Author contributions: Cao Y contributed to the funding acquisition, resources, conceptualization, and supervision; Zhao YC, Li GY, and Cao Y contributed to the methodology; Zhao YC participated in data curation and writing - original draft preparation; Li GY, Chen S, Wang YL, and Feng JY were involved in writing - review and editing; Chen S, Wang YL, and Feng JY contributed to validation; All authors reviewed and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81670948.
Institutional animal care and use committee statement: All procedures were approved the Animal Care Committee of the Capital Medical University of Stomotology and adhered to the institutional and national guidelines for animal welfare (Approval No. KQYY-2024).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Corresponding author: Yu Cao, PhD, Professor, Department of Wangfujing General School of Stomatology, Capital Medical University School of Stomatology, No. 11 Pewter Lane, Dongcheng District, Beijing 100010, China. caoyu_bj@163.com
Received: September 10, 2025 Revised: October 20, 2025 Accepted: January 14, 2026 Published online: February 26, 2026 Processing time: 157 Days and 4.9 Hours
Abstract
BACKGROUND
Mesenchymal stem cells are promising regenerative therapies; however, inflammation often impairs their function. Epiregulin (EREG), a member of the epidermal growth factor family, regulates cell migration, differentiation, and tissue repair. However, its effects on periodontal tissue regeneration using mouse bone marrow stem cells (mBMSCs) under inflammatory conditions remain unclear. We hypothesized that EREG activates epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase 1/2 (ERK1/2) in inflammatory conditions to improve mBMSC function and periodontitis treatment results.
AIM
To investigate EREG’s role in periodontal tissue regeneration, aiming to identify therapeutic targets for periodontal treatment.
METHODS
Tumor necrosis factor alpha stimulates inflammation. Lentiviral short hairpin RNA inhibited EGFR expression. Scratch wounds, Transwell assays, Alizarin Red staining, and Western blotting were used to assess the effects and mechanisms of EREG on the migration, chemotaxis, and osteogenic differentiation capacity of mBMSCs. Micro-computed tomography and histological staining evaluated periodontal tissue regeneration.
RESULTS
EREG enhances the migration, chemotaxis, and osteogenic differentiation of mBMSCs under inflammatory conditions. Mechanistically, EREG binds to EGFR and activates the ERK1/2 signaling pathway to stimulate these functions. Local administration of EREG facilitated periodontal tissue regeneration in a rat model of periodontitis.
CONCLUSION
EREG promotes mBMSC function via the EREG-EGFR-ERK1/2 pathway under inflammatory conditions and facilitates periodontal tissue regeneration.
Core Tip: Enhancing the function of the repaired stem cells in the inflammatory niche is crucial for periodontal tissue regeneration. This study revealed that epiregulin (EREG) enhanced the migration, chemotaxis, and osteogenesis of mouse bone marrow stem cells under inflammatory conditions. Furthermore, EREG activates the extracellular signal-regulated kinase 1/2 pathway by binding to the epidermal growth factor receptor. Disruption of this pathway affected the function of mouse bone marrow stem cells. Finally, the local injection of EREG promoted periodontal tissue regeneration. These findings suggest a novel therapeutic strategy for the treatment of periodontitis.
