1. Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K/Akt pathway delaying intervertebral disc degeneration.
- Author
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Chen HW, Liu MQ, Zhang GZ, Zhang CY, Wang ZH, Lin AX, Kang JH, Liu WZ, Guo XD, Wang YD, and Kang XW
- Subjects
- Aging, Caspase 3 metabolism, Caspase 9 metabolism, Caspase 9 pharmacology, Cells, Cultured, Humans, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Quality of Life, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Protein p53 pharmacology, Tumor Suppressor Protein p53 therapeutic use, bcl-2-Associated X Protein metabolism, bcl-2-Associated X Protein pharmacology, Intervertebral Disc pathology, Intervertebral Disc Degeneration pathology, Nucleus Pulposus pathology, Proanthocyanidins metabolism, Proanthocyanidins pharmacology, Proanthocyanidins therapeutic use
- Abstract
Background: Low back pain is a common symptom of intervertebral disc degeneration (IDD), which seriously affects the quality of life of patients. The abnormal apoptosis and senescence of nucleus pulposus (NP) cells play important roles in the pathogenesis of IDD. Proanthocyanidins (PACs) are polyphenolic compounds with anti-apoptosis and anti-aging effects. However, their functions in NP cells are not yet clear. Therefore, this study was performed to explore the effects of PACs on NP cell apoptosis and aging and the underlying mechanisms of action., Methods: Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. The apoptosis rate was determined TUNEL assays. Levels of apoptosis-associated molecules (Bcl-2, Bax, C-caspase-3 and Caspase-9) were evaluated via western blot. The senescence was observed through SA-β-gal staining and western blotting analysis was performed to observe the expression of senescence-related molecules (p-P53, P53, P21 and P16)., Results: Pretreatment with PACs exhibited protective effects against IL-1β-induced NP cell apoptosis including apoptosis rate, expressions of proapoptosis and antiapoptosis related genes and protein. PACs could also alleviate the increase of p-p53, P21, and P16 in IL-1β-treated NP cells. SA-β-gal staining showed that IL-1β-induced senescence of NP cells was prevented by PACs pertreatment. In addition, PACs activated PI3K/Akt pathway in IL-1β-stimulated NP cells. However, these protected effects were inhibited after LY294002 treatment., Conclusion: The results of the present study showed that PACs inhibit IL-1β-induced apoptosis and aging of NP cells by activating the PI3K/Akt pathway, and suggested that PACs have therapeutic potential for IDD.
- Published
- 2022
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