Identifying chondroprotective diet-derived bioactives and investigating their synergism.
Identifying chondroprotective diet-derived bioactives and investigating their synergism.
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DOI：
10.1038/s41598-018-35455-8
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发表时间：
2018-11-21
影响因子：
4.6
通讯作者：
Clark IM
中科院分区：
文献类型：
--
作者：
Davidson RK;Green J;Gardner S;Bao Y;Cassidy A;Clark IM
骨关节炎（OA）是一种多因素疾病，营养是一个可改变的因素，可能有助于疾病的发作或进展。需要详细了解饮食来源的生物活性分子在OA中发挥作用和相互作用的机制。我们在软骨细胞中使用体外模型分析了96种饮食来源的主要基于植物的生物活性物质，选择了四种候选物质进行进一步研究。我们的目的是确定影响OA关键基因表达的生物活性物质之间的协同相互作用。选择的生物活性物质，萝卜硫素，芹菜素，异甘草素和木犀草素，抑制一种或多种白细胞介素-1诱导的金属蛋白酶参与OA（MMP 1，MMP 13，ADAMTS 4，ADAMTS 5）。异甘草素和毛地黄黄酮对软骨细胞具有活性氧自由基清除活性，而萝卜硫素没有影响，芹菜素仅表现出较弱的趋势。莱菔硫烷抑制IL-1/NFκB和Wnt 3a/TCF/Lef通路，增加TGFβ/Smad 2/3和BMP 6/Smad 1/5/8信号传导。芹菜素对IL-1/NFκB和TGFβ/Smad 2/3通路有较强的抑制作用，而木犀草素对IL-1/NFκB通路仅有较弱的抑制作用。所有四种生物活性物质都抑制了软骨组织外植体中精氨酸诱导的聚集蛋白聚糖损失。萝卜硫素和异甘草素的组合对于抑制软骨细胞中MMP 13基因的表达具有协同作用。我们得出结论，饮食来源的生物活性物质可能是软骨稳态的重要调节剂，生物活性物质之间的协同关系可能具有抗炎和软骨保护作用。
Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role.
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影响因子：
7
作者：
Green, Jonathan A.;Hirst-Jones, Kimberley L.;Clark, Ian M.
通讯作者：
Clark, Ian M.
影响因子：
3.7
作者：
Kang BJ;Ryu J;Lee CJ;Hwang SC
通讯作者：
Hwang SC
影响因子：
4.6
作者：
Balez R;Steiner N;Engel M;Muñoz SS;Lum JS;Wu Y;Wang D;Vallotton P;Sachdev P;O'Connor M;Sidhu K;Münch G;Ooi L
通讯作者：
Ooi L
影响因子：
2.2
作者：
Crasci, Lucia;Cardile, Venera;Panico, Annamaria
通讯作者：
Panico, Annamaria
影响因子：
5.6
作者：
Facchini, Annalisa;Stanic, Ivana;Flamigni, Flavio
通讯作者：
Flamigni, Flavio