End Plate Chondrocyte-Derived Exosomal miR-133a-3p Alleviates Intervertebral Disc Degeneration by Targeting the NF-κB Signaling Pathway through the miR-133a-3p/MAML1 Axis.

Abstract

Chondrocyte-derived exosomes have shown efficacy in differentiating osteoarthritis-affected cartilage. Intervertebral disc degeneration (IVDD) and osteoarthritis often affect facet joints of the spine and show common epidemiological and pathophysiological characteristics. However, the potential of chondrocyte-derived exosomes for treating IVDD remains unclear. The present study aimed to confirm the effect of end plate chondrocyte-derived exosomes (EPC-Exo) on IVDD and elucidate the underlying mechanism. EPC-Exos were isolated and identified by ultracentrifugation, Western blotting, electron microscopy, and nanoparticle tracking analysis. In the in vitro, EPC-Exo uptake by nucleus pulposus (NP) cells reduced cell death by blocking the nuclear factor-κB (NF-κB) signaling pathway. In the in vivo study, EPC-Exos injected into rat intervertebral discs mitigated lipopolysaccharide-induced IVDD, as revealed by a decreased loss of disc height and improved magnetic resonance imaging findings and histological scores. Bioinformatics and sequencing analyses indicated that EPC-Exos alleviated IVDD through the miR-133a-3p/MAML1 axis. The present study suggests that EPC-Exos reduced IVDD incidence via the miR-133a-3p/MAML1 axis-mediated suppression of NF-κB signaling, which prevented the pyroptosis of NP cells.