骨缺损治疗是一医学难题,自体和异体骨移植的诸多限制使人们转向人工骨研究，然而目前人工骨成骨效果仍待提高。我们前期研究表明，载rhBMP-2中空HA微球/CS复合物具有极好的骨修复作用，临床应用潜力很大，但其成骨机理仍不清楚。研究发现，BMP通过依赖和非Smad依赖两条信号通路实现成骨，前者为主，后者为辅。预实验发现p38阻断剂能明显阻断其成骨，因此我们提出假设，该材料是否调控增强非Smad依赖的BMP-2/TAK1/p38/Osx信号通路？此信号通路在该材料介导的骨修复中是否起关键作用？我们拟采用该材料体外诱导MC3T3-E1分化、体内修复骨缺损，检测TAK1、p38、Osx 及成骨标志性基因表达，进行ECT、影像、病理形态等检查，评估骨缺损修复区血供、成骨效果，同时观察加入TAK1、p38抑制剂后对上述指标的影响，旨在探索此信号通路在该材料治疗骨缺损中的作用，为其临床应用提供理论基础。

The regeneration of large bone defect represents a common and significant clinic challenge. Limitations associated with existing treatments such as autologous and allogenic bone grafts have promoted the development of artificial bone graft substitutes. Hollow hydroxyapatite (HA) microsphere/chitosan composite is a novel synthetic bone material recently developed by our collaborator. Our previous work showed that hollow HA microsphere/chitosan composite can be used as a bioactive and osteoconductive carrier for rhBMP-2, showing great capacity to regenerate bone in animal models. This proposal aims to investigate the cellular and molecular mechanism how rhBMP-2 slowly released from hollow HA microsphere/chitosan composite induces new bone formation. The clarification of BMP2 signaling pathways and identification of critical factors in bone repair would help to evaluate the effects of this novel bone material and further explore its clinical utilization.