Wnt5a suppresses inflammation-driven intervertebral disc degeneration via a TNF-α/NF-κB-Wnt5a negative-feedback loop.

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Intervertebral disc degeneration (IVDD) is a complex process driven by inflammation.
• The role of Wnt5a in inflammation-induced IVDD is not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms of Wnt5a in inflammation-driven IVDD.
• To elucidate the signaling pathways regulated by Wnt5a in nucleus pulposus cells.

Main Methods:

• Immunohistochemical staining of human nucleus pulposus (NP) tissues.
• RT-qPCR and Western blotting to assess matrix production.
• siRNA, promoter assays, and inhibitors to study molecular roles and signaling pathways.

Main Results:

• Wnt5a expression correlated with TNF-α in degenerated NP tissues.
• Wnt5a increased aggrecan and collagen II, dependent on JNK-AP1 (JunB) and Sox9.
• Wnt5a inhibited TNF-α-induced MMPs by suppressing NF-κB signaling.
• In vivo studies confirmed Wnt5a's protective role in IVDD.

Conclusions:

• Wnt5a promotes matrix production via Sox9 and antagonizes MMPs via NF-κB inhibition.
• Wnt5a plays a protective role in IVDD through a TNF-α/NF-κB-Wnt5a negative feedback loop.