Specific inhibitory protein Dkk-1 blocking Wnt/β-catenin signaling pathway improve protectives effect on the...

Area of Science:

• Biochemistry
• Cell Biology
• Orthopedics

Background:

• Intervertebral disc degeneration is a significant cause of low back pain.
• The Wnt/β-catenin signaling pathway is implicated in various cellular processes, including cell degeneration.
• Understanding the molecular mechanisms underlying nucleus pulposus cell degeneration is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of the Wnt/β-catenin signaling pathway in nucleus pulposus cell degeneration induced by TNF-α.
• To evaluate the protective effects of Dickkopf-1 (DKK1) on TNF-α-induced nucleus pulposus cell degeneration.

Main Methods:

• Induction of nucleus pulposus cell degeneration using intra-disc injection of TNF-α in a rabbit model.
• Cultured rabbit nucleus pulposus cells were divided into control, degeneration, fluorescence control, and DKK1 intervention groups.
• Detection of key proteins and gene expression (Type II collagen, proteoglycan, β-catenin, MMP-13) using Western blotting, immunocytochemistry, and RT-PCR.

Main Results:

• TNF-α significantly increased β-catenin and MMP-13 expression while inhibiting Type II collagen and proteoglycan synthesis, leading to nucleus pulposus cell degeneration.
• DKK1 treatment significantly reversed the degenerative effects of TNF-α on nucleus pulposus cells.
• Activation of the Wnt/β-catenin signaling pathway by TNF-α was confirmed as a key mechanism in disc degeneration.

Conclusions:

• TNF-α activates the Wnt/β-catenin signaling pathway, leading to increased MMP-13 expression and subsequent intervertebral disc degeneration.
• DKK1 demonstrates a protective effect by blocking the Wnt/β-catenin pathway, preserving the normal metabolism of intervertebral disc tissue.
• The Wnt pathway is a critical regulator in the progression of intervertebral disc degeneration and a potential therapeutic target.