基于Wnt/β-catenin信号通路的γ-生育三烯酚诱导成骨细胞分化的机制研究

项目名称： 基于Wnt/β-catenin信号通路的γ-生育三烯酚诱导成骨细胞分化的机制研究

项目编号： No.31501481

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 农业科学

项目作者： 徐伟丽

作者单位： 哈尔滨工业大学

项目金额： 21万元

中文摘要： 骨质疏松症已成为一个严重的公共健康问题，提高成骨细胞的分化水平是预防骨质疏松症的关键之一。诸多体内研究证实食源性植物化学物γ-生育三烯酚具有优良的成骨活性，是一种全新的具有预防和改善骨质疏松症潜力的天然活性物质。然而，有关γ-生育三烯酚成骨活性的作用机制尚不明确。我们的前期研究表明γ-生育三烯酚可有效地促进成骨细胞分化的早期标志物碱性磷酸酶（ALP）的活性。本项目在前期研究工作基础之上，采用体外细胞培养和分子生物学方法详细阐明γ-生育三烯酚对成骨细胞的诱导分化作用，并应用阻断剂分析在骨形成中起核心作用的Wnt/β-catenin信号通路在γ-生育三烯酚促进成骨细胞分化功能中的作用，在细胞和分子水平上较为系统的阐明γ-生育三烯酚成骨活性的作用机理。该研究结果将为γ-生育三烯酚作为预防骨质疏松症的功能因子在食品领域应用提供重要的理论基础，对于促进和改善骨骼健康的功能性食品的开发具有指导意义。

中文关键词： γ-生育三烯酚；成骨细胞；Wnt/β-catenin信号通路；分化；分子机制

英文摘要： Osteoporosis is a serious public health problem characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. The increase of osteoblast differentiation is one of the key to prevent and treat osteoporosis. Previous in vivo studies showed that γ-tocotrienol (γ-T3) exhibits a strong osteogenic activity. However, the effects of γ-T3 on osteoblast function in vitro and its mechanism have not been reported. The results from our laboratory have demonstrated that and alkaline phosphatase (ALP) activity was enhanced after induction with γ-T3 at 72 h (ALP activity is an early phenotypic marker for osteogenic differentiation of osteoblast). However, the detail role of γ-T3 induced MC3T3-E1 cells differentiation and its mechanisms are not fully understood. In this study, the effect of γ-T3 on the differentiation of MC3T3-E1 cells was investigated. We also analyzed the role of Wnt/β-catenin signaling pathways in γ-T3 regulated the viability and differentiation of osteoblastic MC3T3-E1 cells. The results of the study will be able to provide theoretical support that for the application in food industry production of γ-T3 as functional food ingredients for the prevention of osteoporosis, and will have huge significance for development of functional food products in relation to osteoporosis.

英文关键词： γ-tocotrienol;osteoblast;Wnt/β-catenin signaling pathway;differentiation;mechanism