Dynamic Balance of Histone H3 Methylation: Regulatory Mechanisms and Therapeutic Prospects in RA Immune Dysregulation and Bone Metabolism Imbalance.

OBJECTIVE: To clarify the regulatory mechanisms of the dynamic balance of histone H3 methylation in rheumatoid arthritis (RA) immune dysregulation and bone metabolism imbalance, and to explore related therapeutic approaches. METHODS: We systematically reviewed the roles of key histone H3 methylation sites, including H3K4me3, H3K9me3, and H3K27me3, in RA immune cell activation, inflammatory signaling pathway regulation, and bone cell differentiation. We analyzed the core functions of these sites in the cross-regulation of "immune dysregulation-bone metabolism imbalance" and discussed therapeutic strategies targeting this methylation balance. RESULTS: Accumulating preclinical evidence indicates that the dynamic balance of histone H3 methylation may regulate RA immune cell differentiation imbalance, excessive activation of inflammatory signaling pathways, and the imbalance state where bone resorption exceeds bone formation by modulating the activities of methyltransferases and demethylases. This balance appears to be a key mechanistic link connecting RA immune dysregulation and bone metabolism imbalance. Agents targeting this balance (such as EZH2 inhibitors and Janus kinase [JAK] inhibitors) have shown promising preclinical potential for dual anti-inflammatory and bone-protective effects. CONCLUSION: The dynamic balance of histone H3 methylation emerges as a potential core regulatory hub in the pathological process of RA based on preclinical studies, providing theoretical support for precise diagnosis and treatment of RA. Related targeting strategies may become a new direction to break through the limitations of existing treatments.