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REVIEW ARTICLE

Osteoimmunological effects of macrophages: Mediators that maintain bone homeostasis and function as nanoscale robocops in bone repair

Yiwen Gan1 ,  Jinran Qin1 ,  Xinyi Huang2 ,  Tong Zhao1 ,  Chuanrui Sun3 ,  Liang Wang1 ,  Baoyu Qi3 ,  Kai Sun3,4 ,  Yanming Xie5 ,  Yong Ma1,6 ,  Yili Zhang1* ,  Xu Wei3,4*
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1 Department of Evidence-Based and Translational Medicine, School of Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
2 Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
3 Department of Spine Surgery, Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China
4 Department of Spine Surgery, Institute of Orthopedics of Beijing Integrative Medicine, Beijing, China
5 Department of Evidence-Based Medicine, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
6 Jiangsu CM Clinical Innovation Center of Degenerative Bone and Joint Disease, Wuxi Traditional Chinese Medicine Hospital affiliated to Nanjing University of Chinese Medicine, Wuxi, Jiangsu, China
OTE, 6992 https://doi.org/10.36922/ote.6992
Received: 4 December 2024 | Revised: 16 May 2025 | Accepted: 11 July 2025 | Published online: 21 August 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

The immune system is essential in the regulation of bone metabolic diseases. When immune dysfunction arises, the skeletal system alters its response to immune signals, potentially resulting in bone loss or a heightened risk of fractures. Macrophage activation is considered a critical factor in immunology, tissue homeostasis, disease progression, and inflammation resolution. With ongoing advancements in technology, the use of nanomaterials in combination with macrophages for bone tissue repair has become a highly promising area of research. This review explores the crosstalk between macrophages and their polarized forms, as well as their interactions with bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts. Furthermore, this work emphasizes the critical aspects of using novel nanomaterials that engage macrophages to enhance bone tissue repair. The goal is to underscore the significance of understanding these biological processes in maintaining homeostasis between the skeletal and immune systems, with a particular focus on bone immunology for future research.

Keywords
Macrophages
Bone homeostasis
Nanoscale robocops
Osteoimmunological effects
Funding
The present study was funded by the National Natural Science Foundation of China (grant no. 82174416, 82104977), the Basic Research Program of Jiangsu province (Natural Science Foundation; grant no. BK20220468), the Young Talent Lifting Project of the Chinese Society of Traditional Chinese Medicine (CACM-2022- QNRC2-B28), the Foundation of Jiangsu CM Clinical Innovation Centre of Degenerative Bone & Joint Disease, Jiangsu Science and Education of Traditional Chinese Medicine (2021-No. 4), and the Fundamental Research Funds for the Central Public Welfare Research Institutes (grant no. ZZ13 YQ 039).
Conflict of interest
Yili Zhang is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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