Identification of Targets of a New Nutritional Mixture for Osteoarthritis Management Composed by Curcuminoids Extract, Hydrolyzed Collagen and Green Tea Extract.
Identification of Targets of a New Nutritional Mixture for Osteoarthritis Management Composed by Curcuminoids Extract, Hydrolyzed Collagen and Green Tea Extract.
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DOI：
10.1371/journal.pone.0156902
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Henrotin Y
中科院分区：
文献类型：
--
作者：
Comblain F;Dubuc JE;Lambert C;Sanchez C;Lesponne I;Serisier S;Henrotin Y
我们之前已经证明，姜黄素提取物、水解胶原蛋白和绿茶提取物 (COT) 的混合物可抑制骨关节炎人类软骨细胞的炎症和分解代谢介质的合成。本研究的目的是利用基因组和蛋白质组学方法确定 COT 的新靶点。软骨标本取自 12 名膝骨关节炎患者。将原代人软骨细胞单层培养直至汇合，然后在不存在或存在人白细胞介素(IL)-1β(10-11M)以及使用或不使用COT的情况下温育24或48小时，每种化合物的浓度为4μg/ml。在对照、COT、IL-1β 和 COT IL-1β 条件之间进行微阵列基因表达谱分析。免疫测定用于确认 COT 在蛋白质水平上的作用。超过 4000 个基因在不同条件下表达存在差异。关键的调节途径与炎症、软骨代谢和血管生成有关。 IL-1β 刺激的趋化因子配体 6、基质金属蛋白酶 13、骨形态发生蛋白 2 和斯钙素 1 基因表达和蛋白质产生均被 COT 下调。 COT 显着降低基础条件下斯钙素 1 的产生。 IL-1β 下调 Serpin E1 基因表达和蛋白质产生。 COT逆转IL-1β的抑制作用。在对照条件下，COT 上调 Serpin E1 基因表达。 COT 混合物通过调节关键分解代谢因子、炎症因子和血管生成因子的合成，对骨关节炎的病理生理学产生有益影响。这些发现为使用这些天然成分治疗骨关节炎提供了科学依据。
We have previously demonstrated that a mixture of curcuminoids extract, hydrolyzed collagen and green tea extract (COT) inhibited inflammatory and catabolic mediator’s synthesis by osteoarthritic human chondrocytes. The objective of this study was to identify new targets of COT using genomic and proteomic approaches. Cartilage specimens were obtained from 12 patients with knee osteoarthritis. Primary human chondrocytes were cultured in monolayer until confluence and then incubated for 24 or 48 hours in the absence or in the presence of human interleukin(IL)-1β (10-11M) and with or without COT, each compound at the concentration of 4 μg/ml. Microarray gene expression profiling between control, COT, IL-1β and COT IL-1β conditions was performed. Immunoassays were used to confirm the effect of COT at the protein level. More than 4000 genes were differentially expressed between conditions. The key regulated pathways were related to inflammation, cartilage metabolism and angiogenesis. The IL-1β stimulated chemokine ligand 6, matrix metalloproteinase-13, bone morphogenetic protein-2 and stanniocalcin1 gene expressions and protein productions were down-regulated by COT. COT significantly decreased stanniocalcin1 production in basal condition. Serpin E1 gene expression and protein production were down-regulated by IL-1β. COT reversed the inhibitory effect of IL-1β. Serpin E1 gene expression was up-regulated by COT in control condition. The COT mixture has beneficial effect on osteoarthritis physiopathology by regulating the synthesis of key catabolic, inflammatory and angiogenesis factors. These findings give a scientific rationale for the use of these natural ingredients in the management of osteoarthritis.