Inflammatory Macrophage-derived Itaconate Inhibits DNA Demethylase TET2 to Prevent Excessive Osteoclast Activation in Rheumatoid Arthritis
Itaconic acid, a macrophage-derived metabolite, is significantly elevated in rheumatoid arthritis (RA) patients and plays a crucial role in suppressing osteoclast hyperactivation by inhibiting Tet2 enzyme activity. Exogenous administration of itaconic acid or its derivative, 4-octyl-itaconate, inhibits arthritis progression and mitigates bone destruction, offering a novel therapeutic strategy for RA-associated bone damage. This study highlights itaconic acid as a key regulator in RA pathogenesis, driven by TNF-a to epigenetically control osteoclast activity.