Abstract

Exosomes derived from dental pulp stem cells (DPSCs-Exos) possess potent immunomodulatory properties, but their therapeutic efficacy and underlying mechanisms in intervertebral disc degeneration (IVDD) remain unexplored. Here, we demonstrate that DPSCs-Exos effectively mitigate IVDD through modulation of macrophage polarization, as evidenced by both in vitro and in vivo experiments. Mechanistically, RNA sequencing identified the ERK/MAPK signaling pathway as a key mediator, a finding further validated using the specific ERK inhibitor PD98059. Our results reveal that DPSCs-Exos suppress M1 macrophage polarization and reduce pro-inflammatory cytokine secretion via inhibition of the ERK/MAPK pathway, thereby preserving nucleus pulposus cell function and maintaining extracellular matrix homeostasis. Collectively, this study uncovers a novel regulatory mechanism by which DPSCs-Exos alleviate IVDD and positions them as a promising cell-free therapeutic strategy for treating this debilitating condition.