Apoptosis Signal-Regulated Kinase-1 Promotes Nucleus Pulposus Cell Senescence and Apoptosis to Regulate Intervertebral Disc Degeneration

Abstract

This study investigated the role of apoptosis signal-regulated kinase-1 (ASK1) in intervertebral disc degeneration (IDD). The nucleus pulposus (NP) tissues of non-IDD and IDD patients were subjected to H&E, Safranin-O-fast green, and IHC staining. qRT-PCR was used to assess ASK1 mRNA level within NP tissue samples and cells. CCK-8 assay, SA-β-gal staining, and then flow cytometry were conducted, respectively, to assess the viability, senescence, and apoptosis of NP cells. The extracellular matrix (ECM)-related factors were detected using Western blot analysis. Furthermore, the effect of ASK1 upon the IDD rat model was evaluated through nuclear magnetic resonance imaging (MRI) analysis, HE, Safranin-O-fast green staining, and IHC staining. Finally, JNK inhibitors were utilized to verify the effect of the JNK/p38 signaling on IDD. ASK1 mRNA and protein were upregulated within NP tissue samples from the IDD group, IL-1β-stimulated NP cells, and IDD rats. ASK1 inhibition promoted cell viability and repressed the senescence and apoptosis of NP cells; promoted Collagen II and Aggrecan; inhibited MMP3, MMP9, ADAMTS4, and ADAMTS5 protein levels; and increased NP cells in rat IVD tissues. ASK1 overexpression exerted the opposite effects of ASK1 inhibition upon NP cells. Additionally, JNK/p38 signaling suppression could reverse the ASK1 upregulation-induced dysfunction. In conclusion, ASK1 facilitated the senescence and apoptosis of NP cells in promoting IDD progression, which may be mediated by the JNK/p38 pathway.