Activation of Nell-1 in BMSC Sheet Promotes Implant Osseointegration Through Regulating Runx2/Osterix Axis.
Activation of Nell-1 in BMSC Sheet Promotes Implant Osseointegration Through Regulating Runx2/Osterix Axis.
复制标题
BMSC 片中 Nell-1 的激活通过调节 Runx2/Osterix 轴促进种植体骨整合
DOI：
10.3389/fcell.2020.00868
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发表时间：
2020
影响因子：
5.5
通讯作者：
Yang G
中科院分区：
文献类型：
--
作者：
Lai K;Xi Y;Du X;Jiang Z;Li Y;Huang T;Miao X;Wang H;Wang Y;Yang G
神经表皮生长因子样1蛋白（Neural epidermal growth factor-like 1 protein, Nell-1）首次被研究是因为它与人类颅缝闭锁有关。近年来，由于具有骨诱导能力，Nell-1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。本研究表明，骨髓间充质干细胞薄片中Nell-1的激活促进了体内和体外的骨整合。我们发现过表达Nell-1通过增加Runx2和Osterix的表达来促进骨髓间充质干细胞的成骨分化和基质矿化。激活Nell-1可上调OPG/RANKL的表达比，可能对破骨细胞分化产生负面影响。此外，我们在体内研究中获得了转染过表达和干扰Nell-1的慢病毒的BMSC薄片-种植体复合物，证实了过表达Nell-1促进种植体周围新骨的形成，增加了骨-种植体接触面积百分比。我们的研究结果表明，Nell-1的激活通过调节Runx2/Osterix轴来改善种植体骨整合，并显示了BMSC片-种植体复合物在基因治疗中的潜力。
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.