Friedelin Ameliorates Nucleus Pulposus Inflammation by Increasing p65 Autophagic Degradation to Inhibit NF-κB...

Area of Science:

• Biomedical Science
• Molecular Biology
• Cell Biology

Background:

• Intervertebral disc degeneration (IVDD) is a common condition linked to chronic inflammation, impacting spinal health and quality of life.
• The NF-κB signaling pathway plays a crucial role in mediating inflammatory responses within the intervertebral disc.

Purpose of the Study:

• To investigate the anti-inflammatory effects of Friedelin (FD) on intervertebral disc degeneration (IVDD).
• To elucidate the impact of Friedelin on the NF-κB signaling pathway in the context of IVDD.

Main Methods:

• In vivo studies using cervical intervertebral disc tissue from mice with cervical spine instability.
• In vitro assays utilizing nucleus pulposus (NP) cells.
• Analysis of NF-κB activation, inflammatory cytokine production, and autophagic processes.

Main Results:

• Friedelin treatment significantly reduced NP degeneration and inflammatory cytokine production in IVDD models.
• Friedelin inhibited NF-κB activation by promoting autophagic degradation of p65, independent of IKK activity.
• FD enhanced the interaction between p65 and RNF182, facilitating p65 degradation via autophagy.

Conclusions:

• Friedelin effectively mitigates intervertebral disc degeneration and associated inflammation.
• FD presents a potential therapeutic approach for IVDD by targeting the NF-κB pathway through autophagy-mediated p65 degradation.