Lai Kaichen, Xi Yue, Du Xue, Jiang Zhiwei, Li Yongzheng, Huang Tingben, Miao Xiaoyan, Wang Huiming, Wang Ying, Yang Guoli
The Affiliated Stomatology Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Oral Biomedical Research of Zhejiang Province, Zhejiang University School of Stomatology, Hangzhou, China.
Front Cell Dev Biol. 2020 Sep 22;8:868. doi: 10.3389/fcell.2020.00868. eCollection 2020.
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 and . 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 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）最初因其与人类颅缝早闭的关联而被研究。近年来，由于Nell-1具有骨诱导能力，已被用于加速骨折愈合过程。然而，Nell-1在骨整合过程中的作用尚不清楚。在此我们表明，骨髓间充质干细胞片层中Nell-1的激活促进了骨整合。我们发现，Nell-1的过表达通过增加Runx2和Osterix的表达来改善骨髓间充质干细胞的成骨分化并增强其基质矿化。Nell-1的激活上调了OPG/RANKL的表达比例，这可能对破骨细胞分化有负面影响。此外，在本研究中我们获得了用慢病毒转染过表达和干扰Nell-1的骨髓间充质干细胞片层-植入物复合物，并证实Nell-1的过表达促进了植入物周围的新骨形成并增加了骨-植入物接触面积百分比。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，并显示了骨髓间充质干细胞片层-植入物复合物在基因治疗中的潜力。
