Cadmium-induced annulus fibrosus cell senescence contributes to intervertebral disc degeneration via the JNK/p۵۳ signaling pathway

Objective(s): Investigating the impact of cadmium (Cd) on annulus fibrosus (AF) cells and its potential mechanism was the purpose of the current study.Materials and Methods: Cd was cultivated in different concentrations (۰, ۱, ۵, ۱۰, and ۲۰ μM) on AF cells and the potential effects of the metal were assessed. Using the CCK-۸ method, cell viability and proliferation were identified. Using transcriptome analysis, the annulus fibrosus cells were sequenced both with and without cadmium chloride. The EdU method was used to determine the rate of cell proliferation; senescence-associated β-galactosidase (SA-β-Gal) staining was used to determine the number of positive cells; and western blot, RT-PCR, and immunofluorescence were used to determine the protein and mRNA expression of senescence-associated proteins (p۱۶, p۲۱, and p۵۳) and c-Jun N-terminal kinase (JNK).Results: According to the findings, Cd has the ability to increase the production of senescence-associated genes (p۱۶ and p۲۱) and senescence-associated secreted phenotype (SASP), which includes IL-۱β and IL-۶. Through the JNK/p۵۳ signal pathway, Cd exposure simultaneously accelerated AF cell senescence and promoted SASP. Following JNK inhibitor (SP۶۰۰۱۲۵) treatment, the expression of p۵۳, JNK, and senescence-associated indices were all down-regulated.Conclusion: By activating the JNK/p۵۳ signaling pathway, Cd can induce oxidative stress damage and AF cell senescence. These findings could provide a new approach for treating and preventing intervertebral disc degeneration (IVDD) caused by Cd exposure.

کلیدواژه ها:

Annulus fibrosus ، Cadmium ، c-Jun N-terminal kinase ، Intervertebral disc-degeneration ، Senescence ، Tumor suppressor protein- p۵۳