茶多酚-磷酸钙复合微球的制备及其在高脂微环境下促BMSCs骨向分化的研究

Hyperlipidemia is often accompanied by osteoporosis. When hyperlipidemia patients have bone and other hard tissue repairments, reduced bone (caused by osteoporosis) surroundings will weaken the support of the implant. This seriously affects the repair function of the implant. So far, bone repair materials with good osteoinductive property, which can promote the differentiation of BMSCs into osteoblasts even under high-lipid microenvironment, have rarely been investigated. Our recent studies found that calcium phosphate has osteoinductive property, while tea polyphenol has lipid-lowering effect. However, the behind mechanism is still need further deep investigation. Inorder to research this detailly, we propose the hypothesis of using tea polyphenols-calcium phosphate composed microspheres to promote differentiation of BMSCs into osteoblasts under high-lipid microenvironment. In order to verify this hypothesis, we choose primary BMSCs and bone injury of high fat fed rat as research model. The molecular regulation mechanism of tea polyphenol-calcium phosphate composite microspheres in promoting bone morphogenetic differentiation of BMSCs in high fat microenvironment will be thoroughly researched by using RTPCR, Western blot and RNA interference method. In this study, we will reveal the bone-induced regeneration ability of tea polyphenol-calcium phosphate composite microspheres from the new point of view of "bone induce + lipid lowering", which will provide new materials and new ideas for the repair of hyperlipidemia bone injury.

临床研究发现高脂血症容易导致骨质疏松，引起骨量降低，使损伤周围骨组织对种植体支持作用减弱，严重影响种植体的修复效果。迄今，我们对 “在高脂微环境下，如何使骨修复材料有效促进自体BMSCs骨向分化，实现骨诱导再生功能” 仍知之甚少。我们的预实验结果提示磷酸钙具有骨诱导能力，茶多酚具有降脂作用，但其作用机制还有待进一步探讨。为此，我们提出假说：茶多酚-磷酸钙复合微球在高脂微环境下具有促BMSCs骨向分化的能力。为了验证这一假说，我们将以大鼠原代BMSCs细胞和高脂饲养大鼠及兔的骨损伤为研究模型，采用RTPCR、Western blot、RNA干扰等手段，从分子、细胞、组织以及动物整体水平等多方面探讨、明确茶多酚-磷酸钙复合微球在高脂微环境下促BMSCs骨向分化的调控机制。本研究将从“骨诱导+降脂”这个新视点为揭示茶多酚-磷酸钙复合微球的骨诱导再生能力，为高脂血症骨损伤修复提供新材料、新思路。

临床研究发现高脂血症容易导致骨质疏松，引起骨量降低，使损伤周围骨组织对种植体支持作用减弱，严重影响种植体的修复效果。“在高脂微环境下，如何使骨修复材料有效促进自体BMSCs骨向分化，实现骨诱导再生功能” 是项目研究的关键科学问题。研究结果提示磷酸钙具有骨诱导能力，茶多酚具有降脂作用，并对相关作用机制进行了探讨。项目研究中所得到的茶多酚-磷酸钙复合微球在高脂微环境下具有促BMSCs骨向分化的能力。项目研究工作中以大鼠原代BMSCs细胞和高脂饲养大鼠及兔的骨损伤为研究模型，采用RT-PCR、Western blot、RNA干扰等手段，从分子、细胞、组织以及动物整体水平等多方面探讨、明确了茶多酚-磷酸钙复合微球在高脂微环境下促BMSCs骨向分化的调控机制。项目执行期间取得的重要研究成果如下：1.在项目研究成果的基础上，新获批国家自然科学基金项目1项；2.发表高水平研究论文20篇（其中，中科院一区、二区以上论文16篇）；3.获得辽宁省兴辽英才项目资助；4.获得十二届辽宁青年科技奖；4.获得辽宁省百千万人才工程百人层次称号。本研究从“骨诱导+降脂”这个新视点揭示茶多酚-磷酸钙复合微球的骨诱导再生能力，为高脂血症骨损伤修 复提供了新材料、新思路。