Neural epidermal growth factor-like 1 protein (Nell-1) is first studied because of its association with human craniosynostosis. Nell-1 has been used to accelerate the process of fracture healing because of the osteoinductive ability in recent years. However, the role of Nell-1 during the process of osteointegration is unknown. Here we show that activation of Nell-1 in the BMSC sheet promotes osseointegration in vivo and in vitro. We found that overexpression of Nell-1 improved osteogenic differentiation and enhanced matrix mineralization of BMSCs through increasing expression of Runx2 and Osterix. Activation of Nell-1 up-regulated the expression ratio of OPG/RANKL, which might have a negative influence on osteoclast differentiation. Furthermore, we obtained BMSC sheet-implant complexes transfected with lentivirus overexpressing and interfering Nell-1 in in vivo study, and confirmed that overexpression of Nell-1 promoted new bone formation around the implant and increased the bone-implant contacting area percentage. Our results demonstrate that activation of Nell-1 improves implant osteointegration by regulating Runx2/Osterix axis and shows the potential of BMSC sheet-implant complexes in gene therapy.

神经表皮生长因子样1蛋白（Nell-1）由于其与人类颅突融合症有关而被首次研究。近年来，由于骨诱导能力，Nell-1已被用于加速骨折愈合过程。但是，Nell-1在骨整合过程中的作用尚不清楚。在这里，我们显示激活BMSC表中的Nell-1会促进骨整合体内 和 体外。我们发现，Nell-1的过表达通过增加Runx2和Osterix的表达来改善BMSCs的成骨分化和增强基质矿化。Nell-1的激活上调了OPG / RANKL的表达比例，这可能对破骨细胞的分化产生负面影响。此外，我们获得了慢病毒过度表达和干扰Nell-1转染的BMSC片植入物复合物。体内研究，并证实Nell-1的过度表达促进了植入物周围新骨的形成并增加了骨与植入物的接触面积百分比。我们的结果表明，Nell-1的激活通过调节Runx2 / Osterix轴改善了植入物的骨整合，并显示了BMSC片状植入物复合物在基因治疗中的潜力。