FBXW7 induces apoptosis of nucleus pulposus cells to mediate intervertebral disc degeneration by regulating JNK expression.

OBJECTIVE

To investigate the association between FBXW7 and JNK expression and their roles in regulating nucleus pulposus cell (NPCs) apoptosis in intervertebral disc degeneration (IDD).

METHODS

Firstly, the differentially expressed genes between normal and IDD groups were screened by bioinformatics technology. Subsequently, clinical samples were collected to verify differential gene expression by qPCR and Western blot. Secondly, the effect of FBXW7 on apoptosis of NPCs was verified in vitro. Finally, the therapeutic effect of FBXW7 knockdown on degenerative intervertebral discs was verified by in vivo experiments.

RESULTS

Bioinformatics analysis showed that FBXW7 expression was significantly increased in highly degenerative nucleus pulposus (NP) tissues. Meanwhile, qPCR and Western Blot confirmed that FBXW7 and JNK were upregulated in clinically degenerative NP tissues. On the one hand, transfection of FBXW7 siRNA and JNK siRNA significantly inhibited the apoptosis of NPCs. On the other hand, FBXW7 overexpression upregulated JNK expression, while transfection of JNK siRNA reversed the FBXW7-mediated apoptosis-promoting effect. In vivo experiments further confirmed that FBXW7 shRNA could alleviate the degree of IDD.

CONCLUSIONS

High expression of FBXW7 promotes NPCs apoptosis and accelerates IDD progression by upregulating JNK expression. This study first demonstrates that FBXW7 expression is positively correlated with JNK expression in IDD tissues.