Astaxanthin protects against osteoarthritis via Nrf2: a guardian of cartilage homeostasis
Astaxanthin protects against osteoarthritis via Nrf2: a guardian of cartilage homeostasis
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虾青素通过 Nrf2 预防骨关节炎：软骨稳态的守护者
DOI：
10.18632/aging.102474
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发表时间：
2019-11-30
期刊：
影响因子：
5.2
通讯作者：
Guo, Fengjing
中科院分区：
文献类型：
--
作者：
Sun, Kai;Luo, Jiahui;Guo, Fengjing
范围：骨关节炎（OA）是一种以软骨退化为特征的进行性疾病。虾青素（Astaxanthin，Ast）是一种天然化合物，由于其激活Nrf 2信号传导而具有显著的抗氧化活性和多种医学应用，已被研究用于各种退行性疾病。然而，目前对其治疗OA的功效知之甚少。本研究报告了Ast对OA进展中软骨稳态的影响。方法：应用IL-1β、TNF-α和叔丁基过氧化氢（TBHP）破坏软骨内环境。研究了Ast对Nrf 2信号通路的调节作用，以及损伤相关事件，包括细胞外基质（ECM）降解、炎症、氧化应激、软骨细胞凋亡和体内软骨降解。结果如下：AST通过Nrf 2信号通路抑制OA软骨细胞的ECM降解，通过阻断MAPK信号通路减轻IL-1β诱导的炎症反应和ECM降解。此外，Ast通过抑制NF-κB信号通路，抑制TBHP诱导的氧化应激，从而减轻TNF-α诱导的ECM降解和软骨细胞凋亡。体外结果最终通过证明Ast减轻OA小鼠模型中软骨破坏的严重程度而在体内得到证实。结论：Ast可以通过Nrf 2信号通路保护骨关节炎，这表明Ast可能是OA治疗的潜在治疗补充剂。
Scope: Osteoarthritis (OA) is a progressive disease characterized by cartilage degradation. Astaxanthin (Ast), a natural compound with remarkable antioxidant activity and multiple medical applications due to its activation of Nrf2 signaling, has been studied for application to various degenerative diseases. Currently, however, little is known about its efficacy in treating OA. This study reports the effects of Ast on cartilage homeostasis in OA progression. Methods: IL-1β, TNF-α, and tert-butyl hydroperoxide (TBHP) were used to impair cartilage homeostasis. Modulating effects of Ast on the Nrf2 signaling pathway, and damage-associated events including extracellular matrix (ECM) degradation, inflammation, oxidative stress, chondrocyte apoptosis, and in vivo cartilage degradation were examined. Results: Ast attenuated ECM degradation of OA chondrocytes through the Nrf2 signaling, and ameliorated the IL-1β-induced inflammatory response and ECM degradation via blockade of MAPK signaling. Additionally, Ast alleviated TNF-α-induced ECM degradation and chondrocyte apoptosis by inhibiting the NF-κB signaling, suppressed TBHP-induced oxidative stress, and subsequently reduced chondrocyte apoptosis. In vitro results were finally corroborated in vivo by demonstrating that Ast attenuates the severity of cartilage destruction in a mouse model of OA. Conclusions: Ast could protect against osteoarthritis via the Nrf2 signaling, suggesting Ast might be a potential therapeutic supplement for OA treatment.