MSC-Derived Exosomes Ameliorate Intervertebral Disc Degeneration By Regulating the Keap1/Nrf2 Axis

Area of Science:

• Regenerative Medicine
• Cell Biology
• Biochemistry

Background:

• Intervertebral disc degeneration (IVDD) involves increased reactive oxygen species (ROS) due to reduced Nrf2 expression.
• Bone marrow mesenchymal stem cell derived exosomes (BMSC-exos) are key mediators of intercellular communication, influencing inflammation, apoptosis, and tissue repair.

Purpose of the Study:

• To investigate the therapeutic potential of BMSC-exos in mitigating IVDD by modulating the Keap1/Nrf2 axis.
• To elucidate the mechanisms by which BMSC-exos attenuate oxidative stress and inflammation in nucleus pulposus (NP) cells.

Main Methods:

• Treatment of degenerating NP cells and in vivo models with BMSC-exos.
• Analysis of Keap1, Nrf2, NF-κB expression, and nuclear translocation.
• Assessment of ROS production, apoptosis, inflammation markers, and NP tissue retention.

Main Results:

• BMSC-exos inhibited Keap1 and promoted Nrf2 expression and nuclear translocation in NP cells.
• Treatment with BMSC-exos reduced ROS production, apoptosis, and inflammation.
• In vivo studies showed increased NP tissue retention and expression of Nrf2 and antioxidant proteins in BMSC-exos treated group.

Conclusions:

• BMSC-exos restore the antioxidant response system in degenerating NP cells by modulating the Keap1/Nrf2 axis.
• BMSC-exos represent a promising therapeutic strategy for IVDD by acting as ROS modulators.
• BMSC-exos alleviate IVDD by reducing oxidative stress, inflammation, and apoptosis through the Keap1/Nrf2 pathway.