# DNA methylation and immune regulation in osteoporosis: emerging epigenetic targets for drug discovery

## TL;DR

This paper explores how DNA methylation and immune regulation contribute to osteoporosis and identifies new epigenetic targets for drug development.

## Contribution

The study highlights novel epigenetic targets and non-invasive biomarkers for osteoporosis therapy through DNA methylation and immune regulation.

## Key findings

- Aberrant DNA methylation affects bone metabolism genes and immune cell activity in osteoporosis.
- DNMT inhibitors show preclinical effectiveness in reversing methylation and restoring bone mass.
- Peripheral blood methylation profiles correlate with bone tissue, offering non-invasive diagnostic potential.

## Abstract

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.