Raphanus sativus Linne Protects Human Nucleus Pulposus Cells against H2O2-Induced Damage by Inhibiting TREM2

Biology Pub Date : 2024-08-09 DOI:10.3390/biology13080602
Hyunseong Kim, C. Yeo, Jin Young Hong, Wanjin Jeon, Hyun Kim, Junseong Lee, Yoon Jae Lee, Seung Ho Baek, I. Ha
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Abstract

Intervertebral disc degeneration (IDD) progresses owing to damage and depletion of nucleus pulposus (NP) cells. Cytoprotection mitigates oxidative stress, nutrient deprivation, and mechanical stress, which lead to cell damage and necrosis. We aimed to examine the protective effect of Raphanus sativus Linne (RSL), common radish, against oxidative stress by H2O2 in human NP cells and whether the RSL extracts can inhibit triggering receptor expressed on myeloid cells 2 (TREM2), an inducer of apoptosis and degeneration in NP cells. We administered hydrogen peroxide (H2O2) to cultured human NP cells treated with RSL extracts. We used immunoblotting and quantitative PCR to investigate expression of the apoptosis-associated proteins in cultured cells. RSL significantly enhanced cell survival by suppressing the activation of cleaved caspase-3 and Bax. In contrast, RSL extract increased Bcl2 concentration to downregulate apoptosis. Additionally, RSL treatment notably enhanced the mRNA levels of ACAN and Col2a1 while significantly reducing those of ADAMTS-4, ADAMTS-5, MMP3, and MMP13, key genes involved in NP degeneration. While H2O2 elevated TREM2 expression, causing disc degeneration, RSL downregulated TREM2 expression. Thus, our findings imply that RSL supports human NP cells under oxidative stress and regulates the pathways underlying disc degeneration, particularly TREM2, and that RSL extracts may potentially prevent IDD.
油菜通过抑制 TREM2 保护人类核浆细胞免受 H2O2 引发的损伤
椎间盘变性(IDD)是由于髓核(NP)细胞的损伤和耗竭而导致的。细胞保护可减轻氧化应激、营养匮乏和机械应力等导致细胞损伤和坏死的因素。我们的目的是研究普通萝卜(Raphanus sativus Linne,RSL)对人类 NP 细胞中 H2O2 氧化应激的保护作用,以及 RSL 提取物是否能抑制髓系细胞上表达的触发受体 2(TREM2),TREM2 是 NP 细胞凋亡和变性的诱导因子。我们给用 RSL 提取物处理过的人 NP 细胞注入过氧化氢(H2O2)。我们使用免疫印迹和定量 PCR 技术研究了培养细胞中凋亡相关蛋白的表达情况。通过抑制裂解的 caspase-3 和 Bax 的活化,RSL 明显提高了细胞的存活率。相反,RSL 提取物增加了 Bcl2 的浓度,从而抑制了细胞凋亡。此外,RSL 处理明显提高了 ACAN 和 Col2a1 的 mRNA 水平,同时显著降低了参与 NP 退化的关键基因 ADAMTS-4、ADAMTS-5、MMP3 和 MMP13 的 mRNA 水平。H2O2 会提高 TREM2 的表达,导致椎间盘变性,而 RSL 则会下调 TREM2 的表达。因此,我们的研究结果表明,RSL 能在氧化压力下支持人类 NP 细胞,并调节椎间盘变性的潜在途径,尤其是 TREM2,而且 RSL 提取物有可能预防 IDD。
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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