Proanthocyanidins inhibit the apoptosis and aging of nucleus pulposus cells through the PI3K/Akt pathway delaying intervertebral disc degeneration

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.

KEYWORDS:

• Proanthocyanidins
• apoptosis
• aging
• nucleus pulposus cells
• intervertebral disc degeneration

Acknowledgments

This work was supported by the Special Fund Project for Doctoral Training Programme of Lanzhou University Second Hospital (YJSBD-09), the Municipal Science and Technology Bureau project of Lanzhou (2017-4-60), the Natural science foundation of Gansu Province (20JR5RA325), the Cuiying Applied Basic Research Project of the Second Hospital Medical of Lanzhou University (CY2021-MS-B08), the Cuiying Youth Fund Project of Lanzhou University Second Hospital (CY2021-QN-A06, CY2021-QN-A19), and the Cuiying clinical Top-Technology Project of Lanzhou University Second Hospital (CY2021-BJ-A04). We would like to thank Textcheck (www.textcheck.com) for English language editing.

Authors’ contributions

Hai-Wei.Chen, Ming-Qiang.Liu and Guang-Zhi.Zhang contributed equally to this work, and all authors contributed to the revision and approved the submitted version.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/03008207.2022.2063121