Dietary-Induced Serum Phenolic Acids Promote Bone Growth via p38 MAPK/β-Catenin Canonical Wnt Signaling
Dietary-Induced Serum Phenolic Acids Promote Bone Growth via p38 MAPK/β-Catenin Canonical Wnt Signaling
复制标题
DOI：
10.1002/jbmr.137
复制
发表时间：
2010-11-01
影响因子：
6.2
通讯作者：
Ronis, Martin J. J.
中科院分区：
文献类型：
--
作者：
Chen, Jin-Ran;Lazarenko, Oxana P.;Ronis, Martin J. J.
饮食和营养状况是影响骨发育的关键因素。在本报告中，我们证明了在饲喂蓝莓(BB)的幼年大鼠血清中发现的一种酚酸混合物显着刺激成骨细胞的分化，导致骨量显着增加。在BB饲喂的动物中，较大的骨形成与成骨前体细胞和成骨细胞分化的增加和破骨细胞的生成减少有关。阻断p38的磷酸化消除了BB对成骨前细胞Wnt信号的激活作用，下调了13连环蛋白的表达，也阻断了BB饲喂的大鼠血清在体外刺激成骨细胞分化的能力。根据我们的体内和体外数据，我们提出了Bb的潜在机制这些强大的促骨作用是通过13种连接素的激活以及TCF/Lef基因转录在骨和成骨细胞中的核积累和反式激活来实现的。这些结果表明，P38蛋白激酶(MAPK)/β连接素典型的Wnt信号刺激导致成骨细胞分化的分子事件的刺激导致服用BB饲料的年轻大鼠骨生长显着增加。对BB喂养后血清的LC/MS表征揭示了一种简单的酚酸混合物，这可能为开发一种新的治疗方法来增加峰值骨量和延缓退行性骨质疾病，如骨质疏松(C)2010美国骨与矿物研究协会
Diet and nutritional status are critical factors that influences bone development In this report we demonstrate that a mixture of phenolic acids found in the serum of young rats fed blueberries (BB) significantly stimulated osteoblast differentiation resulting in significantly increased bone mass Greater bone formation in BB diet-fed animals was associated with increases in osteoblast progenitors and osteoblast differentiation and reduced osteoclastogenesis Blockade of p38 phosphorylation eliminated effects of BB on activation of Wnt signaling in preosteoblasts Knocking down 13 catenin expression also blocked the ability of serum from BB diet-fed rats to stimulate osteoblast differentiation in vitro Based on our in vivo and in vitro data we propose that the underlying mechanisms of these powerful bone-promoting effects occur through 13 catenin activation and the nuclear accumulation and transactivation of TCF/LEF gene transcription in bone and in osteoblasts These results indicate stimulation of molecular events leading to osteoblast differentiation triggered by P38 MAP kinase (MAPK)/beta catenin canonical Wnt signaling results in significant increases in bone growth in young rats consuming BB-supplemented diets Liquid chromatography/mass spectrometry (LC/MS) characterization of the serum after BB feeding revealed a mixture of simple phenolic acids that may provide a basis for developing a new treatment to increase peak bone mass and delay degenerative bone disorders such as osteoporosis (C) 2010 American Society for Bone and Mineral Research