Basic Study
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World J Stem Cells. Nov 26, 2024; 16(11): 926-943
Published online Nov 26, 2024. doi: 10.4252/wjsc.v16.i11.926
Yes-associated protein-mediated melatonin regulates the function of periodontal ligament stem cells under oxidative stress conditions
Ke Gu, Xiao-Mei Feng, Shao-Qing Sun, Xing-Yao Hao, Yong Wen
Ke Gu, Xiao-Mei Feng, Shao-Qing Sun, Xing-Yao Hao, Yong Wen, Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan 250012, Shandong Province, China
Ke Gu, Stomatological Hospital, School of Medicine, Nankai University, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin 300041, China
Co-first authors: Ke Gu and Xiao-Mei Feng.
Author contributions: Gu K and Feng XM contributed equally to the manuscript, they are the co-first authors of this manuscript; Feng XM and Wen Y conceived and designed the research; Gu K, Sun SQ, and Hao XY performed the research and acquired the data; Gu K assembled the figures. All authors contributed to the analysis and interpretation of the data and were involved in drafting and revising the manuscript. All authors have read and approved the final manuscript.
Supported by Open Foundation of Shandong Key Laboratory of Oral Tissue Regeneration, No. SDDX202001; Shandong Provincial Natural Science Foundation, No. ZR2021MH075; and Clinical Research Center of Shandong University, No. 2020SDUCRCC006.
Institutional review board statement: This study was approved by the Research Ethics Committee of Shandong University (No. GR201902).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong Wen, Doctor, PhD, Professor, Department of Implantology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44 Wenhua West Road, No. 44-1 Wenhua Road West, Jinan 250012, Shandong Province, China. wenyong@sdu.edu.cn
Received: March 4, 2024
Revised: August 20, 2024
Accepted: September 6, 2024
Published online: November 26, 2024
Processing time: 266 Days and 19.9 Hours
Abstract
BACKGROUND

Human periodontal ligament stem cells (PDLSCs) regenerate oral tissue. In vitro expansion causes replicative senescence in stem cells. This causes intracellular reactive oxygen species (ROS) accumulation, which can impair stem cell function. Tissue engineering efficiency is reduced by exogenous ROS stimulation, which causes premature senescence under oxidative stress. Melatonin (MT), a powerful free radical scavenger, can delay PDLSCs senescence but may not maintain stemness under oxidative stress. This experiment examined the effects of hydrogen peroxide-induced oxidative stress on PDLSCs’ apoptosis, senescence, and stemness.

AIM

To determine if MT can reverse the above effects along with the underlying molecular mechanisms involved.

METHODS

PDLSCs were isolated from human premolars and cultured in different conditions. Flow cytometry was used to characterize the cell surface markers of PDLSCs. Hydrogen peroxide was used to induce oxidative stress in PDLSCs. Cell cycle, proliferation, apoptosis, differentiation, ROS, and senescence-associated β-galactosidase activity were assessed by various assays. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of genes and proteins related to stemness and senescence.

RESULTS

MT increases Yes-associated protein expression and maintains cell stemness in an induced inflammatory microenvironment, which may explain its therapeutic effects. We examined how MT affects PDLSCs aging and stemness and its biological mechanisms.

CONCLUSION

Our study reveals MT’s role in regulating oxidative stress in PDLSCs and Yes-associated protein-mediated activity, providing insights into cellular functions and new therapeutic targets for tissue regeneration.

Keywords: Human periodontal ligament stem cells; Melatonin; Reactive oxygen species; Senescence; Yes-associated protein

Core Tip: While the use of mesenchymal stem cells in preclinical and clinical studies for the treatment of various diseases has provided promising results, the microenvironment of oxidative stress inhibits the efficacy of mesenchymal stem cells-mediated tissue regeneration, which remains a major challenge limiting clinical applications. Our findings provide new insights into melatonin (MT) regulation in the biological functions of oxidative stress-induced periodontal ligament stem cells and elucidate the potential mechanism of Yes-associated protein-mediated MT action. These findings strengthen our comprehension of the role of MT during cellular oxidative stress and provide potential targets for the development of new therapeutic strategies to promote tissue regeneration.