项目名称： 钠钾泵在磷酸钙陶瓷骨诱导过程中的作用及其机制研究

项目编号： No.31500774

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 杨晓

作者单位： 四川大学

项目金额： 20万元

中文摘要： 磷酸钙基陶瓷材料的骨诱导能力已被广泛接受并实际应用于临床骨修复，但其骨诱导能力的细胞和分子生物学水平机理尚未明确。大量文献和前期研究结果表明，钠钾泵的表达量和活性与机体的成骨能力和骨诱导途径密切相关。本项目着眼于材料降解及吸收这一初始细胞事件，拟以耗能钠钾泵为切入点，基于科学事实提出一种全新的钠钾泵介导的钙、磷离子跨膜转运模型。并以此为基础，以研究钠钾泵在骨诱导过程中的作用和机制为目的，通过制备不同降解速率和骨诱导性的磷酸钙材料，初步探索激活钠钾泵离子转运功能的材料学因素；采用多种生化手段调节钠钾泵的活性，结合先进的细胞分子生物学技术、影像学及纳米压痕力学测定技术，从体内外实验角度考察钠钾泵的离子转运功能与间充质干细胞的增殖、黏附、成骨分化以及材料异位成骨能力之间的联系和作用机制。为进一步从细胞和分子水平去深入认识和揭示生物材料骨诱导机制提供实验和理论基础。

中文关键词： 钙磷基生物陶瓷；骨诱导；离子微环境；钠钾泵；间充质干细胞

英文摘要： The Osteoinductivity of calcium phosphate ceramics has been widely accepted and applied in clinical bone defects treatment. However, the cellular and molecular mechanism of how calcium phosphate ceramics contribute to osteoinduction is still unclear. Literature studies and our preliminary experiments show that the expression and activity of sodium-potassium pump (NKA) closely corresponds to osteogenicity and osteoinductivity. In this project, we focus on the primary cellular event related to the degradation and absorption of the calcium phosphate material. According to the function of NKA and scientific evidences, we proposed a transmembrane calcium and phosphate ion transport model which is mediated by NKA. Based on this model, we aim to study the function and mechanism of NKA involved in the osteoinduction process of calcium phosphate ceramics. By using calcium phosphate ceramics of various degradation rate and osteoinductivity, the material factors correlated with the function and activation of NKA mediated ion transport will be explored. Furthermore, stimulation of NKA activity via different methods will be combined with advanced biological, imageologic and nano-mechanical tests to study its effect on mesenchymal stem cells proliferation, adhesion and osteogenic differentiation in vivo and in vitro. Through this project, we hope to provide useful experimental and theoretical foundation to further unveil the cellular and molecular mechanism underlying the osteoinductivity of biomaterials.

英文关键词： calcium phosphate ceramics;osteoinductivity;ionic microenvironment;sodium-potassium pump;mesenchymal stem cells