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

IF 2.8 4区医学 Q3 CELL BIOLOGY

Connective Tissue Research Pub Date : 2022-11-01 DOI:10.1080/03008207.2022.2063121

Hai-Wei Chen, Ming-Qiang Liu, Guang-Zhi Zhang, Cang-Yu Zhang, Zhao-Heng Wang, Ai-Xin Lin, Ji-He Kang, Wen-Zhao Liu, Xu-Dong Guo, Yi-Dian Wang, Xue-Wen Kang

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引用次数: 8

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.

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原花青素通过PI3K/Akt通路抑制髓核细胞凋亡和衰老，延缓椎间盘退变。

背景:腰痛是椎间盘退变(IDD)的常见症状，严重影响患者的生活质量。髓核细胞的异常凋亡和衰老在IDD的发病机制中起重要作用。原花青素是一种具有抗细胞凋亡和抗衰老作用的多酚类化合物。然而，它们在NP细胞中的功能尚不清楚。因此，本研究旨在探讨PACs对NP细胞凋亡和衰老的影响及其作用机制。方法:采用细胞计数试剂盒-8 (CCK-8)法测定细胞活力。TUNEL法测定细胞凋亡率。western blot检测凋亡相关分子(Bcl-2、Bax、C-caspase-3、Caspase-9)水平。SA-β-gal染色观察衰老情况，western blotting分析衰老相关分子(p-P53、P53、P21、P16)的表达情况。结果:PACs预处理对il -1β诱导的NP细胞凋亡具有保护作用，包括凋亡率、促凋亡和抗凋亡相关基因和蛋白的表达。PACs还能缓解il -1β处理的NP细胞中p-p53、P21和P16的升高。SA-β-gal染色结果显示，PACs预处理可抑制il -1β诱导的NP细胞衰老。此外，在il -1β刺激的NP细胞中，PACs激活了PI3K/Akt通路。然而，LY294002处理后，这些保护作用被抑制。结论:本研究结果表明，PACs通过激活PI3K/Akt通路抑制il -1β诱导的NP细胞凋亡和衰老，提示PACs具有治疗IDD的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Connective Tissue Research 生物-细胞生物学

CiteScore

6.60

自引率

3.40%

发文量

审稿时长

2 months

期刊介绍： The aim of Connective Tissue Research is to present original and significant research in all basic areas of connective tissue and matrix biology. The journal also provides topical reviews and, on occasion, the proceedings of conferences in areas of special interest at which original work is presented. The journal supports an interdisciplinary approach; we present a variety of perspectives from different disciplines, including Biochemistry Cell and Molecular Biology Immunology Structural Biology Biophysics Biomechanics Regenerative Medicine The interests of the Editorial Board are to understand, mechanistically, the structure-function relationships in connective tissue extracellular matrix, and its associated cells, through interpretation of sophisticated experimentation using state-of-the-art technologies that include molecular genetics, imaging, immunology, biomechanics and tissue engineering.