TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol
TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol
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DOI：
10.1016/j.bone.2011.10.035
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发表时间：
2012-01-01
期刊：
影响因子：
4.1
通讯作者：
Hong, Jeong-Ho
中科院分区：
文献类型：
--
作者：
Byun, Mi Ran;Jeong, Hana;Hong, Jeong-Ho
山奈酚（KMP）通过调节细胞活动对骨质疏松症和肥胖症发挥保护作用，但其潜在的分子机制尚未完全阐明。 TAZ（具有 PDZ 结合基序的转录共激活因子）通过刺激 RUNX2（runt 相关转录因子 2）的活性并抑制 PPAR gamma（过氧化物酶体增殖物激活受体 gamma）的活性来调节间充质干细胞的成骨细胞和脂肪细胞分化。在这项研究中，我们研究了 KMP 对 TAZ 调节的成骨细胞和脂肪细胞分化的影响。 KMP通过促进TAZ和RUNX2之间的物理相互作用来增加间充质细胞的成骨细胞分化，从而增加RUNX2的转录活性。 KMP 还增强了 TAZ 与 PPAR γ 的关联，从而抑制 PPAR γ 靶标的基因转录，导致脂肪细胞分化减弱。有趣的是，山奈酚对 RUNX2 和 PPAR γ 介导的转录活性的调节作用在 TAZ 缺失的小鼠胚胎成纤维细胞中受损，但通过恢复 TAZ 表达而恢复。我们的结果表明，KMP 增强了 TAZ 活性，从而增强 RUNX2 介导的成骨细胞分化并抑制 PPAR γ 刺激的脂肪细胞分化，表明 KMP 作为通过 TAZ 激活控制骨质流失和肥胖的有效治疗试剂的潜力。 (C) 2011 Elsevier Inc. 保留所有权利。
Kaempferol (KMP) exerts protective effects against both osteoporosis and obesity by regulating cellular activities, but the underlying molecular mechanisms have not been fully elucidated. TAZ (transcriptional coactivator with PDZ-binding motif) modulates both osteoblast and adipocyte differentiation from mesenchymal stem cells by stimulating the activities of RUNX2 (runt-related transcription factor 2) and suppressing the activities of PPAR gamma (peroxisome proliferator-activated receptor gamma). In this study, we investigated the effects of KMP on TAZ regulated osteoblast and adipocyte differentiation. KMP increased the osteoblast differentiation of mesenchymal cells by facilitating the physical interaction between TAZ and RUNX2, thus the increasing transcriptional activities of RUNX2. KMP also enhanced the association of TAZ with PPAR gamma, thereby suppressing the gene transcription of PPAR gamma targets and resulting in diminished adipocyte differentiation. Interestingly, the regulatory effects of kaempferol on RUNX2 and PPAR gamma-mediated transcriptional activity were impaired in TAZ-null mouse embryonic fibroblasts but recovered by restoration of TAZ expression. Our results demonstrate that KMP fortifies TAZ activity, which enhances RUNX2-mediated osteoblast differentiation and suppresses PPAR gamma-stimulated adipocyte differentiation, indicating the potential of KMP as an effective therapeutic reagent for controlling bone loss and adiposity through TAZ activation. (C) 2011 Elsevier Inc. All rights reserved.