α-Tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signaling and bone resorbing activity
α-Tocotrienol inhibits osteoclastic bone resorption by suppressing RANKL expression and signaling and bone resorbing activity
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DOI：
10.1016/j.bbrc.2011.02.085
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发表时间：
2011-03-25
影响因子：
3.1
通讯作者：
Lee, Zang Hee
中科院分区：
文献类型：
--
作者：
Ha, Hyunil;Lee, Jong-Ho;Lee, Zang Hee
维生素E是一种具有强大抗氧化活性的必需营养素，它是两类化合物——生育酚（TPs）和生育三烯醇（TTs）的混合物。尽管Us表现出比α - tp更好的骨保护活性，但其潜在机制尚不清楚。在本研究中，我们研究了α - tt和α - tp是否可以调节破骨细胞骨吸收。我们发现，在IL-1或1 α，25(OH)(2)维生素D-3和前列腺素E-2联合诱导的成骨细胞和骨髓细胞共培养中，α - tt而α - tp抑制破骨细胞的发生。据此，只有α - tt抑制成骨细胞nf - κ B配体受体激活因子（RANKL）的表达。此外，α - tt而非α - tp通过抑制c-Fos表达抑制rankl诱导的破骨细胞向前体分化，可能是通过抑制ERK和NF-kappa B的激活。当c-Fos或活性形式的NFATc1（破骨细胞生成过程中c-Fos的关键下游）过表达时，这种抗破骨细胞作用被逆转。此外，只有α - tt能降低成熟破骨细胞的骨吸收活性，而不影响其存活。总之，我们的研究结果表明，α - tt而不是α - tp通过抑制破骨细胞的分化和活化而具有抗骨吸收特性，这表明α - tt可能在治疗和预防以过度骨破坏为特征的骨病方面具有治疗价值。(C) 2011爱思唯尔公司版权所有。
Vitamin E, an essential nutrient with powerful antioxidant activity, is the mixture of two classes of compounds, tocopherols (TPs) and tocotrienols (TTs). Although Us exhibit better bone protective activity than alpha-TP, the underlying mechanism is poorly understood. In this study, we investigated whether alpha-TT and alpha-TP can modulate osteoclastic bone resorption. We found that alpha-TT but not alpha-TP inhibits osteoclastogenesis in coculture of osteoblasts and bone marrow cells induced by either IL-1 or combined treatment with 1 alpha,25(OH)(2) vitamin D-3 and prostaglandin E-2. In accordance with this, only alpha-TT inhibited receptor activator of NF-kappa B ligand (RANKL) expression in osteoblasts. In addition, alpha-TT but not alpha-TP inhibited RANKL-induced osteoclast differentiation from precursors by suppression of c-Fos expression, possibly through inhibiting ERK and NF-kappa B activation. This anti-osteoclastogenic effect was reversed when c-Fos or an active form of NFATc1, a critical downstream of c-Fos during osteoclastogenesis, was overexpressed. Furthermore, only alpha-TT reduced bone resorbing activity of mature osteoclasts without affecting their survival. Overall, our results demonstrate that alpha-TT but not alpha-TP has anti-bone resorptive properties by inhibiting osteoclast differentiation and activation, suggesting that alpha-TT may have therapeutic value for treating and preventing bone diseases characterized by excessive bone destruction. (C) 2011 Elsevier Inc. All rights reserved.