Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes.
Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes.
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DOI：
10.1186/ar2700
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发表时间：
2009
影响因子：
4.9
通讯作者：
Haqqi TM
中科院分区：
文献类型：
--
作者：
Rasheed Z;Anbazhagan AN;Akhtar N;Ramamurthy S;Voss FR;Haqqi TM
骨关节炎 (OA) 的主要危险因素是衰老，但人们对这种风险背后的机制知之甚少。与年龄相关的晚期糖基化终末产物 (AGE) 的积累可以激活软骨细胞并诱导促炎细胞因子和基质金属蛋白酶 (MMP) 的产生。在本研究中，我们研究了表没食子儿茶素-3-没食子酸酯 (EGCG) 对 AGE 修饰的 BSA (AGE-BSA) 诱导的人 OA 软骨细胞中 TNFα 和 MMP-13 的激活和产生的影响。人软骨细胞通过酶消化从 OA 软骨中获得，并用体外产生的 AGE-BSA 刺激。通过定量RT-PCR测量TNFα和MMP-13的基因表达。使用细胞因子特异性 ELISA 测定培养基中的 TNFα 蛋白。使用蛋白质免疫印迹法分析培养基中 MMP-13 的产生、丝裂原激活蛋白激酶 (MAPK) 的磷酸化以及 NF-κB 的激活。使用高度灵敏和特异性的 ELISA 测定 NF-κB p65 的 DNA 结合活性。使用体外激酶活性测定法测定 IκB 激酶 (IKK) 活性。通过明胶酶谱法测定培养基中的MMP-13活性。 EGCG 显着降低人软骨细胞中 AGE 刺激的基因表达以及 TNFα 和 MMP-13 的产生。 EGCG 对 AGE-BSA 诱导的 TNFα 和 MMP-13 表达的抑制作用至少部分是通过抑制 p38-MAPK 和 JNK 激活来介导的。此外，在体外活性测定中，EGCG 抑制 IKKβ 激酶的磷酸化活性，并且 EGCG 通过抑制细胞质中抑制蛋白 IκBα 的降解，抑制 AGE 介导的 NF-κB 激活和 DNA 结合活性。 EGCG 对 AGE-BSA 刺激的人 OA 软骨细胞的这些新药理作用提供了新的建议，即 EGCG 或 EGCG 衍生化合物可能通过抑制人软骨细胞中 AGE 介导的激活和分解代谢反应来抑制软骨降解。
The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age-related accumulation of advanced glycation end products (AGEs) can activate chondrocytes and induce the production of proinflammatory cytokines and matrix metalloproteinases (MMPs). In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG) on AGE-modified-BSA (AGE-BSA)-induced activation and production of TNFα and MMP-13 in human OA chondrocytes. Human chondrocytes were derived from OA cartilage by enzymatic digestion and stimulated with in vitro-generated AGE-BSA. Gene expression of TNFα and MMP-13 was measured by quantitative RT-PCR. TNFα protein in culture medium was determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the MMP-13 production in the culture medium, phosphorylation of mitogen-activated protein kinases (MAPKs), and the activation of NF-κB. DNA binding activity of NF-κB p65 was determined using a highly sensitive and specific ELISA. IκB kinase (IKK) activity was determined using an in vitro kinase activity assay. MMP-13 activity in the culture medium was assayed by gelatin zymography. EGCG significantly decreased AGE-stimulated gene expression and production of TNFα and MMP-13 in human chondrocytes. The inhibitory effect of EGCG on the AGE-BSA-induced expression of TNFα and MMP-13 was mediated at least in part via suppression of p38-MAPK and JNK activation. In addition, EGCG inhibited the phosphorylating activity of IKKβ kinase in an in vitro activity assay and EGCG inhibited the AGE-mediated activation and DNA binding activity of NF-κB by suppressing the degradation of its inhibitory protein IκBα in the cytoplasm. These novel pharmacological actions of EGCG on AGE-BSA-stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG-derived compounds may inhibit cartilage degradation by suppressing AGE-mediated activation and the catabolic response in human chondrocytes.
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DOI：
10.1124/jpet.103.059220
发表时间：
2004-02-01
影响因子：
3.5
作者：
Ahmed, S;Wang, NZ;Haqqi, TM
通讯作者：
Haqqi, TM
影响因子：
--
作者：
Loeser, RF;Yammani, R;Yan, SD
通讯作者：
Yan, SD
影响因子：
3.8
作者：
Bin Hafeez, Bilal;Ahmed, Salahuddin;Haqqi, Tariq M.
通讯作者：
Haqqi, Tariq M.
DOI：
10.1186/1750-4732-3-1
发表时间：
2009-01-06
期刊：
Osteopathic medicine and primary care
影响因子：
--
作者：
Fendrick, A Mark;Greenberg, Bruce P
通讯作者：
Greenberg, Bruce P
DOI：
10.1073/pnas.96.8.4524
发表时间：
1999-04-13
影响因子：
11.1
作者：
Haqqi, TM;Anthony, DD;Mukhtar, H
通讯作者：
Mukhtar, H