Ceramide accumulation accelerates nucleus pulposus cells degradation by p38MAPK activation.

Ceramide is a lipid molecule that regulates life activities such as cell differentiation, proliferation, apoptosis, and aging. However, whether ceramide plays a role in the intervertebral disc degeneration (IDD) is not clear. The aim of this study is to explore the effect of ceramide during the nucleus pulposus (NP) cells degeneration. We used human NP cells and passaged them until the fourth generation to analyze the content of ceramide. Cell-permeable C6-ceramide was used to upregulate ceramide expression, and myriocin was used to inhibit the accumulation of ceramide. To understand the relation between p38MAPK and ceramide, SB203580 was used to inhibit the activation of p38MAPK. We tested the viability of NP cells by the detection of collagen II and p16 expression, the proliferation, and the apoptosis of NP cells. Ceramide content was increased in NP cells from passage 1 (P1) to P4. The upregulation of ceramide accelerated the P1 NP cell degeneration by the reduction of collagen II production and proliferative cells population, increased p16 expression, and apoptotic cells population. However, the suppression of ceramide delayed the degeneration of P4 NP cells in the previous aspects. The accumulation of ceramide activated the phosphorylation of p38MAPK, and the inhibition of p38MAPK activation also alleviated the C6-ceramide-induced NP cell degeneration. Ceramide accumulates during NP cell degradation, and the upregulated ceramide contributes to the NP cells degeneration by p38MAPK activation.