Effects of quercetin, a natural phenolic compound, in the differentiation of human mesenchymal stem cells (MSC) into adipocytes and osteoblasts
Effects of quercetin, a natural phenolic compound, in the differentiation of human mesenchymal stem cells (MSC) into adipocytes and osteoblasts
复制标题
DOI：
10.1016/j.jnutbio.2016.03.005
复制
发表时间：
2016-06-01
影响因子：
5.6
通讯作者：
Manuel Quesada-Gomez, Jose
中科院分区：
文献类型：
--
作者：
Casado-Diaz, Antonio;Anter, Jaouad;Manuel Quesada-Gomez, Jose
天然酚类可能具有对抗氧化应激的有益特性，氧化应激与衰老和主要的慢性衰老相关疾病有关，例如骨矿物质质量损失（骨质疏松症）和糖尿病。本研究的主要目的是分析槲皮素，一种主要的营养化合物存在于“地中海饮食”，对间充质干细胞（MSC）分化的影响。在两种槲皮素浓度（0.1和10 M）的存在下，诱导这些细胞分化成成骨细胞或脂肪细胞。几个生理参数和成骨细胞和脂肪形成标记基因的表达进行了监测。槲皮素（10 μ M）抑制细胞增殖，碱性磷酸酶（ALPL）活性和矿化，下调ALPL，胶原蛋白I型α 1（COL 1A 1）和骨钙素[骨γ-羧基谷氨酸蛋白（BGln）]成骨细胞生成相关基因在MSC分化成骨细胞的表达。此外，在这些培养物中，诱导CCAAT/增强子结合蛋白α（CEBPA）和过氧化物酶体增殖物激活受体γ 2（PPARG 2）成脂基因，并观察到细胞分化为脂肪细胞。槲皮素不影响增殖，但增加脂肪形成，主要是在10 μ M的浓度在MSC诱导分化为脂肪细胞。在槲皮素处理的培养物中，β-和γ-连环蛋白（plalcoglobin）核水平分别降低和升高。这表明高浓度的槲皮素对MSC成骨细胞和脂肪形成分化的作用是通过Wnt/β-连环蛋白抑制介导的。总之，槲皮素补充抑制成骨细胞分化和促进脂肪形成在最高测试浓度。高浓度槲皮素的这种可能的不利影响应考虑到在营养或药物策略使用这样的黄酮醇。(C)2016 Elsevier Inc. All rights reserved.
Natural phenols may have beneficial properties against oxidative stress, which is associated with aging and major chronic aging-related diseases, such as loss of bone mineral mass (osteoporosis) and diabetes. The main aim of this study was to analyze the effect of quercetin, a major nutraceutical compound present in the "Mediterranean diet", on mesenchymal stem-cell (MSC) differentiation. Such cells were induced to differentiate into osteoblasts or adipocytes in the presence of two quercetin concentrations (0.1 and 10 M). Several physiological parameters and the expression of osteoblastogenesis and adipogenesis marker genes were monitored. Quercetin (10 mu M) inhibited cell proliferation, alkaline phosphatase (ALPL) activity and mineralization, down-regulating the expression of ALPL, collagen type I alpha 1 (COL1A1) and osteocalcin [bone gamma-carboxyglutamate protein (BGLAP)] osteoblastogenesis-related genes in MSC differentiating into osteoblasts. Moreover, in these cultures, CCAAT/enhancer-binding protein alpha (CEBPA) and peroxisome proliferator-activated receptor gamma 2 (PPARG2) adipogenic genes were induced, and cells differentiated into adipocytes were observed. Quercetin did not affect proliferation, but increased adipogenesis, mainly at 10-mu M concentration in MSC induced to differentiate to adipocytes. beta- and gamma-catenin (plalcoglobin) nuclear levels were reduced and increased, respectively, in quercetin-treated cultures. This suggests that the effect of high concentration of quercetin on MSC osteoblastic and adipogenic differentiation is mediated via Wnt/beta-catenin inhibition. In conclusion, quercetin supplementation inhibited osteoblastic differentiation and promoted adipogenesis at the highest tested concentration. Such possible adverse effects of high quercetin concentrations should be taken into account in nutraceutical or pharmaceutical strategies using such flavonol. (C) 2016 Elsevier Inc. All rights reserved.