Mangiferin Attenuates Osteoclastogenesis, Bone Resorption, and RANKL-Induced Activation of NF-κB and ERK
Mangiferin Attenuates Osteoclastogenesis, Bone Resorption, and RANKL-Induced Activation of NF-κB and ERK
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DOI：
10.1002/jcb.22800
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Xu, Jiake
中科院分区：
文献类型：
--
作者：
Ang, Estabelle;Liu, Qian;Xu, Jiake
骨质疏松等溶解性骨病有一个共同的病理特征，即破骨细胞骨吸收超过骨合成。破骨细胞的形成和活化受核因子κ B配体受体激活因子（RANKL）的调控。RANKL信号通路的诱导发生在RANKL与其同源受体RANK相互作用之后。这种特异性结合驱动下游信号通路的激活；最终诱导破骨细胞的形成和激活。在这项研究中，我们发现一种天然免疫调节剂芒果苷通过减弱rankl诱导的信号传导抑制破骨细胞的形成和骨吸收。芒果苷降低破骨细胞标记基因的表达，包括组织蛋白酶K、降钙素受体、DC-STAMP和v - atp酶d2。机制研究表明，芒果苷抑制rankl诱导的nf - κ B活化，同时抑制I κ B- α降解和p65核易位。此外，芒果苷对rankl诱导的ERK磷酸化也有抑制作用。总的来说，我们的数据表明芒果苷具有抗骨吸收特性，这表明芒果苷在治疗和预防涉及过度破骨细胞骨吸收的骨病方面具有潜在的应用前景。j .细胞。生物化学学报，2011,31(2):389 - 397。(C) 2010 Wiley-Liss, Inc。
Osteolytic bone diseases such as osteoporosis have a common pathological feature in which osteoclastic bone resorption outstrips bone synthesis. Osteoclast formation and activation are regulated by receptor activator of nuclear factor kappa B ligand (RANKL). The induction of RANKL-signaling pathways occurs following the interaction of RANKL to its cognate receptor, RANK. This specific binding drives the activation of downstream signaling pathways; which ultimately induce the formation and activation of osteoclasts. In this study, we showed that a natural immunomodulator, mangiferin, inhibits osteoclast formation and bone resorption by attenuating RANKL-induced signaling. Mangiferin diminished the expression of osteoclast marker genes, including cathepsin K, calcitonin receptor, DC-STAMP, and V-ATPase d2. Mechanistic studies revealed that mangiferin inhibits RANKL-induced activation of NF-kappa B, concomitant with the inhibition of I kappa B-alpha degradation, and p65 nuclear translocation. In addition, mangiferin also exhibited an inhibitory effect on RANKL-induced ERK phosphorylation. Collectively, our data demonstrates that mangiferin exhibits anti-resorptive properties, suggesting the potential application of mangiferin for the treatment and prevention of bone diseases involving excessive osteoclastic bone resorption. J. Cell. Biochem. 112: 89-97, 2011. (C) 2010 Wiley-Liss, Inc.