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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
WDR36 inhibits the osteogenic differentiation and migration of periodontal ligament stem cells
Yi Wang, Feng-Qiu Zhang, Zhi-Peng Fan, Xin-Ling Zhu, Wan-Hao Yan, Xiu-Li Zhang
Yi Wang, Department of Wangfujing General School of Stomatology, Capital Medical University, Beijing 100070, China
Feng-Qiu Zhang, Department of Periodontics School of Stomatology, Capital Medical University, Beijing 100070, China
Zhi-Peng Fan, Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Beijing 100070, China
Zhi-Peng Fan, Beijing Laboratory of Oral Health, Capital Medical University, Beijing 100070, China
Zhi-Peng Fan, Research Unit of Tooth Development and Regeneration, Chinese Academy of Medical Sciences, Beijing 100070, China
Xin-Ling Zhu, Department of Periodontology, Hangzhou Stomatology Hospital, Hangzhou 310006, Zhejiang Province, China
Wan-Hao Yan, Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100070, China
Xiu-Li Zhang, Department of Stomatology, Civil Aviation General Hospital, Beijing 100123, China
Co-corresponding authors: Feng-Qiu Zhang and Zhi-Peng Fan.
Author contributions: Wang Y wrote the manuscript; Zhang FQ and Fan ZP conceptualized the study, revised and formatted the content of the manuscript, and verified spelling, punctuation, and grammatical errors; Wang Y, Zhu XL, Yan WH, and Zhang XL carried out the experiments and analyzed the data. The collaboration between Zhang FQ and Fan ZP was essential for the publication of this manuscript. Both authors contributed equally to the research, including study design, revised and formatted the content of the manuscript, and verified spelling, punctuation, and grammatical errors. This statement confirms that both Zhang FQ and Fan ZP share equal responsibility and contribution as co-corresponding authors of this work. All authors contributed to the preparation of the manuscript.
Supported by Beijing Natural Science Foundation, No. 7192076.
Institutional review board statement: Institutional review board approval was not needed for this study because the cells used in this study were commercially obtained from LMAI Bio Company (Shanghai, China), which complies with all relevant ethical guidelines for cell procurement and distribution. These cells were further modified by surface marking in our laboratory for the purposes of this research. As no human or animal subjects were involved in the collection of the cells used, no additional ethical approval was required.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: The datasets generated during the current work are available from the corresponding authors on reasonable request.
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: Feng-Qiu Zhang, Department of Periodontics School of Stomatology, Capital Medical University, No. 9 Fanjiacun Road, Fengtai District, Beijing 100070, China.
zhfengqiu@126.com
Received: July 23, 2024
Revised: November 23, 2024
Accepted: January 16, 2025
Published online: February 26, 2025
Processing time: 215 Days and 18.2 Hours
BACKGROUND
Periodontitis is an inflammatory disease caused by the host’s immune response and various interactions between pathogens, which lead to the loss of connective tissue and bone. In recent years, mesenchymal stem cell (SC) transplantation technology has become a research hotspot, which can form periodontal ligament, cementum, and alveolar bone through proliferation and differentiation.
AIM
To elucidate the regulatory effects of WD repeat-containing protein 36 (WDR36) on the senescence, migration, and osteogenic differentiation of periodontal ligament SCs (PDLSCs).
METHODS
The migration and chemotaxis of PDLSCs were detected by the scratch-wound migration test and transwell chemotaxis test. Alkaline phosphatase (ALP) activity, Alizarin red staining, calcium content, and real-time reverse transcription polymerase chain reaction (RT-qPCR) of key transcription factors were used to detect the osteogenic differentiation function of PDLSCs. Cell senescence was determined by senescence-associated β-galactosidase staining.
RESULTS
The 24-hour and 48-hour scratch-wound migration test and 48-hour transwell chemotaxis test showed that overexpression of WDR36 inhibited the migration/chemotaxis of PDLSCs. Simultaneously, WDR36 depletion promoted the migration/chemotaxis of PDLSCs. The results of ALP activity, Alizarin red staining, calcium content, and RT-qPCR showed that overexpression of WDR36 inhibited the osteogenic differentiation of PDLSCs, and WDR36 depletion promoted the osteogenic differentiation of PDLSCs. Senescence-associated β-galactosidase staining showed that 0.1 μg/mL icariin (ICA) and overexpression of WDR36 inhibited the senescence of PDLSCs, and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.
CONCLUSION
WDR36 inhibits the migration and chemotaxis, osteogenic differentiation, and senescence of PDLSCs; 0.1 μg/mL ICA inhibits the senescence of PDLSCs. Therefore, WDR36 might serve as a target for periodontal tissue regeneration and the treatment of periodontitis.
Core Tip: Periodontal ligament stem cells (PDLSCs) are an important cell source for periodontal tissue regeneration. They can migrate to injured areas to promote tissue repair, induce osteogenic differentiation for bone tissue regeneration, and delay tissue loss by inhibiting senescence. In this study, we investigated the regulatory function of WD repeat-containing protein 36 (WDR36) on PDLSCs and found that WDR36 inhibited the migration, osteogenic differentiation, and senescence of PDLSCs. Thus, WDR36 may serve as a new candidate target for periodontal tissue regeneration.
