Nell-1在脊柱融合中的实验研究进展

Experimental Research Progress of Nell-1 in Spinal Fusion

摘要: 背景：随着再生医学的发展，自体骨移植、异体骨移植、骨形态发生蛋白(Bone morphogenetic protein, BMPS)等现有的骨移植物应用于脊柱融合越来越普遍，对不良反应少的新型骨诱导因子的需求也日益增加。Nel样分子(Nel-like Molecular type I, Nell-1)是一种新型骨诱导生长因子，在骨骼的生长发育中起到重要作用。与BMPS相比，Nell-1尽管不能在成纤维细胞中成骨，但可以在小鼠肌肉模型中诱导骨髓基质细胞(Mesenchymal stem cells, BMSC)形成骨，并且能够逆转BMPs所产生的异位骨、脂肪生成等不良反应，表明Nell-1蛋白更具有特异性。Nell-1作为一种新型骨诱导生长因子有望在脊柱融合中表现出巨大的优势。方法：由第一作者检索百度学术、PubMed、Web of Science及中国知网收录的相关文献，中文检索词为“脊柱融合；Nell-1；动物实验模型；支架；协同作用”，英文检索词为“Spinal fusion; Nell-1; Animal experimental model; Bracket; Synergies”，最后纳入45篇文献进行综述。总结和结论：通过对关于Nell-1对脊柱融合的实验研究进行相关总结分析，发现Nell-1有促进脊柱融合的潜力，但仍然存在缺乏最佳给药途径、分子机制不完全清楚、是否存在与应用相关的不良反应等不足之处，但其具有促进成骨细胞分化、血管生成等特点，相信以后随着技术的发展进一步研究分子机制、优化剂量和方案、探索与其他成骨生长因子及干细胞的联合应用，有望将Nell-1促进脊柱融合的潜力实现大型动物模型成熟化，进而转向临床实践。

Abstract: With the development of regenerative medicine, existing bone grafts such as autologous bone transplantation, allogeneic bone transplantation, and bone morphogenetic protein (BMPS) are in-creasingly used in spinal fusion, and the demand for new bone inducing factors with fewer adverse reactions is also increasing. Nel-like Molecular Type I (Nell-1) is a novel bone inducing growth factor that plays an important role in the growth and development of bones. Compared with BMPS, alt-hough Nell-1 cannot form bone in fibroblasts, it can induce bone formation by bone marrow stromal cells (BMSC) in a mouse muscle model, and can reverse adverse reactions such as ectopic bone and adipogenesis produced by BMPs, indicating that Nell-1 protein is more specific. Nell-1, as a novel bone inducing growth factor, is expected to exhibit significant advantages in spinal fusion. Methods: The first author searched the relevant literature collected by Baidu Academic, PubMed, Web of Science, and CNKI. The Chinese key words were “Spinal fusion; Nell-1; Animal experimental model; Stents; Synergies”, and the English key words were “Spinal fusion; Nell-1; Animal experimental model; Brackets; Synergies”. Finally, 45 articles were included for review. Summary and Conclusion: Based on the summary and analysis of experimental studies on Nell-1 for spinal fusion, it is found that Nell-1 has the potential to promote spinal fusion, but there are still shortcomings such as the lack of optimal drug delivery routes, unclear molecular mechanisms, and whether there are ad-verse reactions related to application. However, it has the characteristics of promoting osteoblast differentiation and angiogenesis. It is believed that with the development of technology in the fu-ture, further research on molecular mechanisms, optimization of doses and protocols, and explora-tion of joint applications with other osteogenic growth factors and stem cells are expected to mature the potential of Nell-1 to promote spinal fusion in large animal models, and then turn to clinical practice.