Sulforaphane Protects Human Chondrocytes Against Cell Death Induced by Various Stimuli
Sulforaphane Protects Human Chondrocytes Against Cell Death Induced by Various Stimuli
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DOI：
10.1002/jcp.22506
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发表时间：
2011-07-01
影响因子：
5.6
通讯作者：
Flamigni, Flavio
中科院分区：
文献类型：
--
作者：
Facchini, Annalisa;Stanic, Ivana;Flamigni, Flavio
软骨细胞死亡可导致关节疾病，如骨关节炎（OA）的软骨变性。萝卜硫素（SFN）是一种从十字花科食物中提取的天然化合物，众所周知，它是一种抗癌物质，但根据最近的证据，它还显示出对多种非肿瘤细胞的细胞保护作用。因此，我们在体外测试了SFN保护软骨细胞免于细胞死亡的能力。用SFN在低微分子范围内处理人C-28/I2软骨细胞单层培养物数天，可降低细胞生长，但不影响细胞存活或诱导细胞凋亡。然而，它降低了C-28/I2软骨细胞暴露于刺激下的细胞死亡，先前报道的刺激可迅速引发细胞凋亡，即细胞因子肿瘤坏死因子-a （TNF）加环己亚胺（CHX）或多胺类似物N(1)， N(11) -二乙基去精胺（DENSPM）加CHX。特别是SFN预处理降低了效应物和引发物caspase活性以及JNK激酶的相关激活。SFN甚至对H(2)O(2)具有细胞保护作用，与之前的刺激不同，H(2)O(2)诱导细胞死亡，但没有产生明显的半胱天冬酶激活。SFN预处理还可以阻止生长相关癌基因a （GRO α，一种促凋亡趋化因子）刺激的OA软骨细胞三维微块培养中caspase的激活。微团块中caspase活性的抑制似乎与p38 MAPK磷酸化的抑制有关。总之，本研究表明，低微分子SFN浓度在多种实验条件下对软骨细胞系和OA软骨细胞施加一系列死亡刺激，发挥促存活和抗凋亡作用，并影响信号通路。j .细胞。中国生物医学工程学报，2011,31(2):379 - 379。(C) 2010 Wiley-Liss, Inc。
Chondrocyte cell death can contribute to cartilage degeneration in articular diseases, such as osteoarthritis (OA). Sulforaphane (SFN), a natural compound derived from cruciferous aliment, is well known as an anti-carcinogen, but according to recent evidence it also shows cytoprotective effects on a variety of non-tumoral cells. Therefore we have tested the ability of SFN to protect chondrocytes from cell death in vitro. Treatment of growing monolayer cultures of human C-28/I2 chondrocytes with SFN in the low micro-molecular range for a few days, reduced cell growth without affecting cell survival or inducing apoptosis. However it decreased cell death in C-28/I2 chondrocytes exposed to stimuli previously reported to promptly trigger apoptosis, that is, the cytokine tumor necrosis factor-a (TNF) plus cycloheximide (CHX) or the polyamine analogue N(1), N(11) -diethylnorspermine (DENSPM) plus CHX. In particular pre-treatment with SFN reduced effector and initiator caspase activities and the associated activation of JNK kinases. SFN exerted a cytoprotective action even versus H(2)O(2), which differently from the previous stimuli induced cell death without producing an evident caspase activation. SFN pre-treatment also prevented caspase activation in three-dimensional micromass cultures of OA chondrocytes stimulated with growth-related oncogene a (GRO alpha), a pro-apoptotic chemokine. The suppression of caspase activation in micromasses appeared to be related to the inhibition of p38 MAPK phosphorylation. In conclusion, the present work shows that low micro-molecular SFN concentrations exert pro-survival and anti-apoptotic actions and influence signaling pathways in a variety of experimental conditions employing chondrocyte cell lines and OA chondrocytes treated with a range of death stimuli. J. Cell. Physiol. 226: 1771-1779, 2011. (C) 2010 Wiley-Liss, Inc.