Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis

Abstract

Background: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. Objective: To explore IDD pathogenesis at the cellular and gene levels and investigate lactotransferrin (LTF) expression in IDD patients and its possible mechanism. Methods: We downloaded the IDD data set from the Gene Expression Omnibus (GEO) database, screened the differentially expressed genes (DEGs) and hub genes and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to construct a protein–protein interaction (PPI) network. Subsequently, we verified LTF's regulatory mechanism through cell experiments. IL-1β was used to intervene in nucleus pulposus cells (NPCs) to construct the IDD cell model, and LTF and Fas expression was detected by qRT–PCR. LTF inhibitor, Fas inhibitor, LTF mimic, and Fas mimic were used to intervene in each group. Western blotting was used to detect Fas, Caspase-3, Bax, and Bcl-2 expression. Results: A total of 131 DEGs and 10 hub genes were screened. LTF mRNA in the IDD model was significantly higher than that in the control group, while Fas' mRNA was significantly lower. When LTF was upregulated or downregulated in NPCs, apoptosis marker expression showed the opposite trend. The rescue test showed that LTF and Fas' overexpression greatly enhanced NPC apoptosis. Conclusion: LTF promotes IDD progression by regulating Fas in NPCs, and it may be an effective gene therapy target.

LTF induces senescence and degeneration in the meniscus via the NF-κB signaling pathway: A study based on integrated bioinformatics analysis and experimental validation

“…Various studies have reported that excessive activation of NF-κB could induce the progression of nearly all aging-related diseases, and inhibition of NF-κB, in contrast, could reverse SASP and aging ( García-García et al, 2021 ; Zhang X. B. et al, 2022 ).…”