Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway.
Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway.
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DOI：
10.1016/j.intimp.2023.110159
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发表时间：
2023-04
影响因子：
5.6
通讯作者：
Guihe Yang;Xiaoyang Liu;Xingzhi Jing;Jinjin Wang;Heran Wang;Feifei Chen;Wenchao Wang;Yuandong Shao;Xingang Cui
中科院分区：
文献类型：
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作者：
Guihe Yang;Xiaoyang Liu;Xingzhi Jing;Jinjin Wang;Heran Wang;Feifei Chen;Wenchao Wang;Yuandong Shao;Xingang Cui
研究背景软骨终板（CEP）退变是导致椎间盘退变（IVDD）的重要始动因素。虾青素（Ast）是一种天然脂溶性红橙色类胡萝卜素，在多种生物体中具有多种生物活性，包括抗氧化、抗炎和抗衰老作用。然而，Ast 对终板软骨细胞的作用和机制仍知之甚少。本研究的目的是探讨Ast对CEP变性的影响及其潜在分子机制。方法采用叔丁基过氧化氢(TBHP)模拟IVDD病理环境。我们研究了 Ast 对 Nrf2 信号通路和损伤相关事件的影响。通过手术切除L4后部元件构建IVDD模型，探讨Astin在体内的作用。结果我们发现Ast增强Nrf-2/HO-1信号通路的激活，从而促进线粒体自噬过程，抑制氧化应激和CEP软骨细胞铁焦亡，最终改善细胞外基质（ECM）降解、CEP钙化和终板软骨细胞凋亡。使用 siRNA 敲低 Nrf-2 可抑制 Ast 诱导的线粒体自噬过程及其保护作用。此外，Ast 抑制氧化刺激诱导的 NF-κB 活性，并可以改善炎症反应。体内实验也证实了Ast可以减轻IVDD的发育和CEP钙化。结论Ast可以通过激活Nrf-2/HO-1通路来保护椎体软骨终板免受氧化应激和退化。我们的结果表明 Ast 可以作为 IVDD 进展和治疗的潜在治疗剂。
BackgroundCartilage endplate (CEP) degeneration is an important initiating factor leading to intervertebral disc degeneration (IVDD). Astaxanthin (Ast) is a natural lipid-soluble and red–orange carotenoid which possesses various biological activities, including antioxidant, anti-inflammatory, and anti-aging effects in multiple organisms. However, the effects and mechanism of Ast on endplate chondrocytes remain largely unknown. The objective of the current study was to investigate the effects and of Ast on CEP degeneration and its underlying molecular mechanisms.MethodsTert-butyl hydroperoxide (TBHP) was used to mimic the IVDD pathological environment. We investigated the effects of Ast on the Nrf2 signaling pathway and damage-associated events. The IVDD model was constructed by surgical resection of L4 posterior elements to explore the role of Astin vivo.ResultsWe found that the activation of the Nrf-2/HO-1 signaling pathway was enhanced by Ast, thus promoted mitophagy process, inhibited oxidative stress and CEP chondrocytes ferroptosis, eventually ameliorated extracellular matrix (ECM) degradation, CEP calcification and endplate chondrocytes apoptosis. Knockdown of Nrf-2 using siRNA inhibited Ast induced mitophagy process and its protective effect. Moreover, Ast inhibited oxidative stimulation-induced NF-κB activity and could ameliorate the inflammation response. The results also were confirmed by experimentsin vivo, Ast alleviated IVDD development and CEP calcification.ConclusionsAst could protect vertebral cartilage endplate against oxidative stress and degeneration via activating Nrf-2/HO-1 pathway. Our results imply that Ast may serve as a potential therapeutic agent for IVDD progression and treatment.