Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. May 26, 2024; 16(5): 560-574
Published online May 26, 2024. doi: 10.4252/wjsc.v16.i5.560
Effects of interleukin-10 treated macrophages on bone marrow mesenchymal stem cells via signal transducer and activator of transcription 3 pathway
Meng-Hao Lyu, Ce Bian, Yi-Ping Dou, Kang Gao, Jun-Ji Xu, Pan Ma
Meng-Hao Lyu, Jun-Ji Xu, Department of Periodontics, School of Stomatology, Capital Medical University, Beijing 100050, China
Ce Bian, Department of Orthodontics, School of Stomatology, Capital Medical University, Beijing 100050, China
Yi-Ping Dou, Kang Gao, Pan Ma, Department of Dental Implantology, School of Stomatology, Capital Medical University, Beijing 100050, China
Jun-Ji Xu, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing 100050, China
Jun-Ji Xu, Beijing Laboratory of Oral Health, Capital Medical University, Beijing 100050, China
Co-first authors: Meng-Hao Lyu and Ce Bian.
Co-corresponding authors: Jun-Ji Xu and Pan Ma.
Author contributions: Lyu MH, Bian C, Xu JJ, and Ma P designed the research; Lyu MH and Bian C performed the research; acquired and analyzed data form experiments and wrote the original draft; Dou YP and Gao K contributed new reagents/analytic tools; Lyu MH and Bian C revised the manuscript and edited the final version of the manuscript; Xu JJ and Ma P provided financial support and ensured the final manuscript, and they are the co-corresponding authors of this manuscript; Lyu MH and Bian C contributed equally to the work; and all authors have read and approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 81974153 and No. 82122015; and Beijing Natural Science Foundation, No. L222088.
Institutional animal care and use committee statement: The study was approved by the Animal Ethical and Welfare Committee of Beijing Stomatological Hospital Affiliated to Capital Medical University. The approval number is KQYY-2022.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at mapanxw@163.com.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Pan Ma, PhD, Professor, Department of Dental Implantology, School of Stomatology, Capital Medical University, No. 4 Tiantan Xili, Beijing 100050, China. mapanxw@163.com
Received: December 29, 2023
Revised: February 26, 2024
Accepted: April 12, 2024
Published online: May 26, 2024
Processing time: 146 Days and 22.9 Hours
Abstract
BACKGROUND

Alveolar bone defects caused by inflammation are an urgent issue in oral implant surgery that must be solved. Regulating the various phenotypes of macrophages to enhance the inflammatory environment can significantly affect the progression of diseases and tissue engineering repair process.

AIM

To assess the influence of interleukin-10 (IL-10) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) following their interaction with macrophages in an inflammatory environment.

METHODS

IL-10 modulates the differentiation of peritoneal macrophages in Wistar rats in an inflammatory environment. In this study, we investigated its impact on the proliferation, migration, and osteogenesis of BMSCs. The expression levels of signal transducer and activator of transcription 3 (STAT3) and its activated form, phosphorylated-STAT3, were examined in IL-10-stimulated macrophages. Subsequently, a specific STAT3 signaling inhibitor was used to impede STAT3 signal activation to further investigate the role of STAT3 signaling.

RESULTS

IL-10-stimulated macrophages underwent polarization to the M2 type through substitution, and these M2 macrophages actively facilitated the osteogenic differentiation of BMSCs. Mechanistically, STAT3 signaling plays a crucial role in the process by which IL-10 influences macrophages. Specifically, IL-10 stimulated the activation of the STAT3 signaling pathway and reduced the macrophage inflammatory response, as evidenced by its diminished impact on the osteogenic differentiation of BMSCs.

CONCLUSION

Stimulating macrophages with IL-10 proved effective in improving the inflammatory environment and promoting the osteogenic differentiation of BMSCs. The IL-10/STAT3 signaling pathway has emerged as a key regulator in the macrophage-mediated control of BMSCs’ osteogenic differentiation.

Keywords: Macrophages; Interleukin-10; Bone marrow mesenchymal stem cells; Signal transducer and activator of transcription 3; Inflammatory response

Core Tip: This study investigated the mechanism of interleukin-10 (IL-10) affecting macrophages in inflammatory environments, observed the effects of different macrophages on the biological behavior and osteogenic differentiation of bone marrow mesenchymal stem cells, and found that IL-10/signal transducer and activator of transcription 3 signaling plays a crucial role in promoting bone formation by affecting macrophages. This study provides a new strategy for solving the problem of poor osteogenesis in bone defect repair caused by an excessive inflammatory response in clinical work.