很多正颌与颅面手术都需要易获取和可靠的骨移植材料。然而目前作为骨移植金标准的自体骨移植，在髂嵴取骨常伴发供区疼痛、步态异常等多种不良后果，且颅骨抑制物的感染损伤与血肿常使自体移植物达不到理想的成骨效果，因此亟需更好的方案改善其在骨组织修复临床的应用。利用成骨诱导分子促进骨组织损伤原位修复是解决骨自体移植问题的一个好方法。现有多篇Nell-1蛋白显著促进骨再生特性的研究被报道。Nell-1蛋白成骨诱导能力可以被用于骨形成和再生的多种状况（如牙槽骨移植，颅面骨牵张成骨和部分长骨缺损修复等）。我们最新克隆发现的Nell-1新型转录本Nell-1ΔE具有更显著的成骨诱导能力，并存在着区别于Nell-1蛋白诱导成骨的信号转导机制。继续深入研究Nell-1ΔE蛋白的功能，不断探索新的成骨诱导因子的功能机制将有助于发现更安全、有效的临床治疗方法，最终使新分子骨形成作用的潜力能应用到转化医学研究。

Readily available and reliable bone graft material is essential for many orthopedic and craniofacial surgeries. The current gold standard for bone graft material is autologous bone. However associated donor site morbidity including pain, gait disturbance, thigh paresthesia for iliac crest donor sites, and infection, neurologic deficits, and hematomas for calvarial grafts make autograft harvest less than ideal. Thus, there is a critical need for better autograft alternatives. There are many translational studies on Nell-1's significant bone regeneration properties that complement our present work for this proposal. From a therapeutic standpoint, the osteoinductive properties of Nell-1 can be applied to situations where bone formation and regeneration are required (e.g., alveolar bone grafting, craniofacial distraction osteogenesis, spinal fusion, segmental long bone defects). Excitingly, our preliminary data suggests that Nell-1ΔE, which is a new transform of Nell-1, may be an even more potent osteoinductive agent than Nell-1 through the different signal pathways. this proposal addresses a practical need to further understand the function and mechanism of Nell-1 isoforms and fulfills our long term objective to identify, harness, and channel novel molecules that induces excess bone formation during craniofacial growth into reliable clinical therapies to regenerate bone.