REVIEW article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
This article is part of the Research TopicAdvancements in Pharmacological Treatments for Bone Metabolic DiseasesView all 6 articles
DNA Methylation and Immune Regulation in Osteoporosis: Emerging Epigenetic Targets for Drug Discovery
Provisionally accepted
- 1Women's Hospital School of Medicine Zhejiang University, Hangzhou, China
- 2Hangzhou First People's Hospital, Hangzhou, China
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Osteoporosis (OP) is a complex skeletal disease characterized by the disruption of bone homeostasis, with immune dysregulation identified as a significant pathogenic cause. The interaction between immune cells and bone cells within the bone marrow microenvironment affects osteoclast (OC) activation and osteoblast (OB) function through cytokine networks，including RANKL/OPG and Wnt signaling. Aberrant DNA methylation, a significant epigenetic change, influences osteoporosis by regulating the expression of genes associated with bone metabolism (e.g., RUNX2, NFATc1, SOST) and modifying immune cell activities, thereby facilitating inflammatory bone loss. Increased DNA methyltransferase (DNMT) activity has been associated with osteoimmune dysregulation, oxidative stress, and heightened bone resorption. Inhibiting DNMT inhibitors (DNMTi) has shown effectiveness in preclinical animals by reversing abnormal methylation patterns and restoring bone mass. Additionally, DNA methylation profiles generated from peripheral blood exhibit significant concordance with bone tissue methylation, presenting prospective non-invasive biomarkers for OP diagnosis, prognosis, and therapy monitoring of OP. Incorporating epigenetic profiling into clinical practice could facilitate precision medicine strategies for OP, combining immune regulation with targeted DNA methylation therapy. This study emphasizes the relationship between DNA methylation and osteoimmunity, delineating innovative treatment targets and biomarker prospects to enhance OP therapy.
Keywords: Osteoporosis, DNA Methylation, Osteoblasts, Osteoclasts, Immune Regulation
Received: 19 Aug 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Yang, Cai, Zhuge, Yao and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yao Yao, yaoyaofb@zju.edu.cn
Caihong Zheng, chzheng@zju.edu.cn
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