Ceramide accumulation accelerates nucleus pulposus cells degradation by p38MAPK activation

Area of Science:

• Biochemistry
• Cell Biology
• Orthopedics

Background:

• Ceramides are critical lipid molecules regulating cellular processes like differentiation, proliferation, apoptosis, and aging.
• The specific role of ceramides in intervertebral disc degeneration (IDD) remains largely unexplored.

Purpose of the Study:

• To investigate the effect of ceramide accumulation on nucleus pulposus (NP) cell degeneration.
• To elucidate the underlying molecular mechanisms, particularly the involvement of p38MAPK signaling.

Main Methods:

• Human NP cells were cultured and treated with C6-ceramide (to upregulate) or myriocin (to inhibit ceramide).
• The p38MAPK pathway was inhibited using SB203580.
• Cell viability (collagen II, p16 expression), proliferation, and apoptosis were assessed.

Main Results:

• Ceramide content increased with NP cell passaging (P1 to P4).
• Elevated ceramide accelerated NP cell degeneration, reducing collagen II, decreasing proliferation, and increasing apoptosis and p16 expression.
• Ceramide accumulation activated p38MAPK phosphorylation; inhibiting p38MAPK mitigated ceramide-induced degeneration.

Conclusions:

• Ceramide accumulates during NP cell degeneration.
• Upregulated ceramide exacerbates NP cell degeneration, mediated through p38MAPK activation.