I am a
Home I AM A Search Login

Papers of the Week


Papers: 16 Nov 2024 - 22 Nov 2024


2024 Nov 16


Int Immunopharmacol


39550843


143


Pt 3

Endplate chondrocyte-derived exosomal miR-128-3p mitigates intervertebral disc degeneration by targeting TRAF6 via the miR-128-3p/TRAF6 axis to suppress pyroptosis.

Authors

Li Q, Guo R, Wu Z, Zhao C, Chen X, Wang H, Shen C

Abstract

Intervertebral disc degeneration (IVDD) is a leading cause of chronic back pain and significantly impacts quality of life. The pathogenesis of IVDD is largely driven by inflammation, pyroptosis, and extracellular matrix (ECM) degradation, which current therapies fail to adequately address. In this study, we explore the therapeutic potential of exosomes derived from endplate chondrocytes (EPCs), with a particular focus on the microRNA miR-128-3p. Our findings reveal that exosomes isolated from third-generation EPCs, enriched with miR-128-3p, exhibit potent anti-inflammatory and anti-pyroptotic effects in lipopolysaccharide-treated nucleus pulposus cells, which are key contributors to IVDD pathology. Specifically, we demonstrate that miR-128-3p delivered via EPC-derived exosomes directly targets TRAF6, effectively suppressing activation of the NF-κB signaling pathway, which is known to play a pivotal role in inflammation and ECM breakdown, leading to a marked reduction in pro-inflammatory cytokine release and mitigation of ECM degradation. Importantly, third-generation EPC exosomes, with higher levels of miR-128-3p, showed superior efficacy compared to fifth-generation EPCs, underscoring the critical role of miR-128-3p in mediating these protective effects. Our research highlights the promise of EPC-derived exosomes, particularly those rich in miR-128-3p, as a novel, cell-free therapeutic approach for IVDD. Unlike current treatments that focus primarily on symptom management, our approach targets key molecular pathways underlying IVDD progression, including inflammation, pyroptosis, and ECM degradation. By elucidating the miR-128-3p/TRAF6 axis, this study provides a foundation for the development of targeted, biologically based interventions aimed at halting or even reversing IVDD, thereby offering hope for more effective and lasting therapeutic options.