Effect of interferon-gamma stimulation on the transcriptome of RANKL/M-CSF-induced osteoclasts

To delineate the direct transcriptional consequences of IFN-γ exposure during terminal osteoclast differentiation, we performed RNA sequencing on RANKL/M-CSF-induced osteoclasts treated with or without IFN-γ.

Differential expression analysis identified a suite of IFN-γ-responsive genes and revealed significant perturbation of pathways governing osteoclast fusion and bone resorption. Notably, we identified Lipocalin-2 (Lcn2) as a key downstream effector whose expression is robustly induced by IFN-γ. These data elucidate the molecular mechanisms by which IFN-γ translates immune signals into pro-osteoclastogenic instructions, highlighting a specific transcriptional program that enhances osteoclast differentiation and may contribute to inflammatory bone loss.