牙种植需求增大，术区骨量欠佳时面临骨结合不良等挑战。局部骨膜具有再生能力，可修复骨缺损，而NICD作为Notch通路核心分子与骨缺损修复密切相关；同时，Hippo通路效应分子YAP有望通过NICD诱导成骨，但有关YAP-NICD轴对骨膜成骨及种植体周骨代谢的影响未见报道。课题组前期发现，YAP信号和Notch通路与骨膜细胞成骨及种植体骨结合有关。基于此，本课题以骨膜为切入点，体外探究YAP信号和Notch通路对骨膜细胞行为的影响；同时，以YAP-NICD信号为靶环节，结合CRISPR/Cas9及基因过表达技术，揭示Notch通路在YAP等信号支配下，级联调控骨膜成骨的潜在机制；体内构建种植体植入模型，采用活体荧光示踪及基因蛋白检测技术等，进一步探究二者参与种植体周骨代谢的内在机理。研究成果有望为局部骨量欠佳时的种植治疗提供新思路，为骨结合不良所致的种植体失败提供有效策略，具有深远应用前景。

There is an increasing demand for dental implant. However, it is faced with poor osseointegration and other challenges when patients are lack of local bone volume. Periosteum has remarkable capability of bone regeneration, which plays a crucial role in bone healing. In fact, Notch signaling has been shown to relate to the bone healing process. Meanwhile, Hippo signaling effector YAP is expected to control Notch signaling interactions to regulate and induce osteogenesis. So far, the effect of YAP-NICD axis on periosteal osteogenesis and peripheral bone metabolism around dental implants has not been reported. Our previous studies indicated that both Notch signaling and YAP are related to osteogenic differentiation of periosteum-derived cells, and YAP is related to implant osseointegration. Therefore, we focus our attention on periosteum. We plan to first explore the influence of Notch signaling and YAP effector on the biological behavior of periosteum-derived cells. Then, we expect to reveal underlying molecular mechanism of Notch signaling cascaded regulating periosteum-derived cells osteogenesis controlled by Hippo signaling effector YAP. We combine CRISPR/Cas9 technique and gene overexpression technology to obtain related target genes differential expressions in periosteum-derived cells. Furthermore, animal models with dental implant insertion will be established in order to explain internal mechanisms between YAP and Notch signaling, involved in the bone metabolism around dental implant. Various gene and protein detection techniques and live fluorescence tracing will be adopted in these animal studies. The results of this program will hopefully provide new train of thought and therapeutic strategy to dental implant patients with limited bone volume, as well as provide effective solutions to implant failure caused by poor osseointegration.