MAPK信号参与钙磷基纳米粒子诱导成骨系细胞自噬调控成骨分化的机制研究

项目名称： MAPK信号参与钙磷基纳米粒子诱导成骨系细胞自噬调控成骨分化的机制研究

项目编号： No.81501861

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王任先

作者单位： 北京市创伤骨科研究所

项目金额： 18万元

中文摘要： 纳米羟基磷灰石（NanoHAP）在骨再生中促进成骨系细胞的黏附、增殖和分化，但NanoHAP粒子调控成骨系细胞功能的分子机制尚缺乏深入的研究。依据纳米粒子具有诱导细胞自噬的共性、细胞自噬关键基因通过MAPK信号通路调控成骨分化等研究成果以及我们的研究基础，提出以下假说“NanoHAP诱导成骨系细胞发生自噬进而通过MAPK信号通路调控成骨特异转录因子Osterix的表达来促进成骨分化”。为验证这一假说，本项目拟采用纳米材料学、细胞学以及分子生物学的先进技术方法，研究NanoHAP粒子对成骨系细胞自噬的影响，探讨细胞自噬影响成骨系细胞分化的关键信号通路，从而探明NanoHAP粒子与细胞相互作用过程中细胞自噬及MAPK信号通路的调控机制，此项目如能成功实施将对钙磷基纳米材料在骨修复及再生中的生物学功效提供更深入的理论依据。

中文关键词： 纳米羟基磷灰石；细胞自噬；MAPK；成骨分化

英文摘要： Nano hydroxyapatite (NanoHAP) could promote cell attachment, proliferation and differentiation in bone regeneration, however, the underline molecular mechanisms is still not very clear. Recently, nanoparticles were defined as a novel class of autophagy activators and autophagy plays a pivotal role in skeletal cell homeostasis. It reported that an important autophagy-related gene leads to osteoblast differentiation through a mechanism involving elevated and prolonged MAPK activity. Thus, we hypothesize that osteoblast autophagy induced by NanoHAP and Ca2+ could promote osteoblast differentiation through MAPK signaling pathway which could regulate the expression of osterix. To test this hypothesis, the nano material science, cytology and molecular biology will be used to confirm the hypothesis comprehensively. The effect of NanoHAP on osteoblast autophagy will be studied. The key biological signal pathway MAPK of osteoblast autophagy regulates osteoblast differentiation will also be studied. Then elucidate the mechanisms that autophagy and MAPK regulate osteoblast differentiation. The successful implementation of the project will help to evaluate the effects of nanomaterial for bone repair and regeneration.

英文关键词： Nano-Hydroxyapatite;cell autophagy;MAPK; osteoblast differentiation