Tea Polyphenols Inhibit Rat Osteoclast Formation and Differentiation

Tea Polyphenols Inhibit Rat Osteoclast Formation and Differentiation
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DOI:
10.1254/jphs.11082fp
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发表时间:
2012-01-01
影响因子:
3.5
通讯作者:
Oguchi, Katsuji
Oguchi, Katsuji
中科院分区:
医学3区
文献类型:
--
作者:
Oka, Yoshiomi;Iwai, Shinichi;Oguchi, Katsuji

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基质金属蛋白酶(MMPs)在与骨和软骨相关的基质变性中起重要作用。破骨细胞活性的调节在骨质疏松症和类风湿性关节炎等骨病的治疗中是必不可少的。绿茶中的多酚,特别是表没食子儿茶素-3-没食子酸酯(EGCG),抑制MMPs的表达和活性。然而,红茶多酚茶黄素-3,3'-二二酸酯(TFDG)对破骨细胞和MMP活性的影响尚不清楚。因此,我们检测了TFDG和EGCG是否影响体外MMP活性和破骨细胞的形成和分化。在大鼠破骨细胞前体细胞和成熟破骨细胞培养中分别加入TFDG或EGCG(10和100 μ M)。与对照组相比,多酚处理的培养物中多核破骨细胞和肌动蛋白环的数量减少。与对照组相比,TFDG-和egcg处理的大鼠破骨前体细胞中MMP-2和MMP-9活性较低。与对照破骨细胞相比,tfdg处理的破骨细胞中MMP-9 mRNA水平显著下降。TFDG和EGCG通过抑制MMPs抑制破骨细胞的形成和分化。TFDG可能比EGCG更有效地抑制肌动蛋白环的形成。因此,TFDG和EGCG可能是治疗骨吸收疾病的合适药物或先导化合物。
Matrix metalloproteinases (MMPs) play an important role in degeneration of the matrix associated with bone and cartilage. Regulation of osteoclast activity is essential in the treatment of bone disease, including osteoporosis and rheumatoid arthritis. Polyphenols in green tea, particularly epigallocatechin-3-gallate (EGCG), inhibit MMPs expression and activity. However, the effects of the black tea polyphenol, theaflavin-3,3'-digallate (TFDG), on osteoclast and MMP activity are unknown. Therefore, we examined whether TFDG and EGCG affect MMP activity and osteoclast formation and differentiation in vitro. TFDG or EGCG (10 and 100 mu M) was added to cultures of rat osteoclast precursors cells and mature osteoclasts. Numbers of multinucleated osteoclasts and actin rings decreased in polyphenol-treated cultures relative to control cultures. MMP-2 and MMP-9 activities were lower in TFDG- and EGCG-treated rat osteoclast precursor cells than in control cultures. MMP-9 mRNA levels declined significantly in TFDG-treated osteoclasts in comparison to control osteoclasts. TFDG and EGCG inhibited the formation and differentiation of osteoclasts via inhibition of MMPs. TFDG may suppress actin ring formation more effectively than EGCG. Thus, TFDG and EGCG may be suitable agents or lead compounds for the treatment of bone resorption diseases.