N-Cadherin Attenuates High Glucose-Induced Nucleus Pulposus Cell Senescence Through Regulation of the ROS/NF-κB Pathway

Abstract

Background/Aims: Diabetes mellitus (DM) is a potential etiology of disc degeneration. N-cadherin (N-CDH) helps maintain the cell viability, cell phenotype and matrix biosynthesis of nucleus pulposus (NP) cells. Here, we mainly aimed to investigate whether N-CDH can attenuate high glucose-induced NP cell senescence and its potential mechanism. Methods: Rat NP cells were cultured in a base culture medium and base culture medium with a 0.2 M glucose concentration. Recombinant lentiviral vectors were used to enhance N-CDH expression in NP cells. Senescence-associated β-galactosidase (SA-β-Gal) activity was measured by SA-β-Gal staining. NP cell proliferation was evaluated by CCK-8 assay. Telomerase activity and intracellular reactive oxygen species (ROS) content were tested by specific chemical kits according to the manufacturer’s instructions. G0/G1 cell cycle arrest was evaluated by flow cytometry. Real-time PCR and Western blotting were used to analyze mRNA and protein expressions of senescence markers (p16 and p53) and matrix macromolecules (aggrecan and collagen II). Additionally, p-NF-κB expression was also analyzed by Western blotting to evaluate NF-κB pathway activity. Results: High glucose significantly decreased N-CDH expression, increased ROS generation and NF-κB pathway activity, and promoted NP cell senescence, which was reflected in the increase in SA-β-Gal activity and senescence marker (p16 and p53) expression, compared to the control group. High glucose decreased telomerase activity and cell proliferation potency. However, N-CDH overexpression partially attenuated NP cell senescence, decreased ROS content and inhibited the activation of the NF-κB pathway under the high glucose condition. Conclusion: High glucose decreases N-CDH expression and promotes NP cell senescence. N-CDH overexpression can attenuate high glucose-induced NP cell senescence through the regulation of the ROS/ NF-κB pathway. This study suggests that N-CDH is a potential therapeutic target to slow DM-mediated disc NP degeneration.

TGF-β mediates aortic smooth muscle cell senescence in Marfan syndrome

“…Although the potential mechanisms underlying cellular senescence are not yet fully understood, it is known that elevated levels of reactive oxygen species (ROS) are associated with the induction of cellular senescence [10, 12]. NF-κB activation also appears to signal induction of cellular senescence in various cell types, including VSMCs [13, 14]. Moreover, increasing ROS levels can activate NF-κB signaling to release senescence-associated secretory phenotype (SASP) factors, which, in turn, further stimulate cellular senescence [15].…”

Small Extracellular Vesicles Derived from Adipocytes Attenuate Intervertebral Disc Degeneration in Rats by Rejuvenating Senescent Nucleus Pulposus Cells and Endplate Cells by Delivering Exogenous NAMPT

“…Given that the components of the NP are mainly determined by the secretion of NPCs, the decline in the function of senescent NPCs significantly affects the load-bearing and buffering of the spine. Improving NPC senescence can significantly promote matrix homeostasis and delay IVDD [ 24 , 25 ]. However, EP is crucial for the IVD nutrient supply.…”

Liraglutide inhibits the apoptosis of human nucleus pulposus cells induced by high glucose through PI3K/Akt/caspase-3 signaling pathway

“…Recent basic and epidemiological studies have shown that DM is an important etiological factor of disc degeneration [4,23]. Previously, some studies demonstrated that HG could cause negative effects on disc cell’s biology, such as inducing disc cell apoptosis and senescence [24,25], and oxidative injury was a vital mechanism participating in the detrimental effects [26]. In our study, the HG group exhibited a significant increase in the formation of ROS levels and higher apoptosis rate of NPCs compared with the control group, which were consistent with previous findings.…”