骨与其他组织的再生往往需要种子细胞、支架材料和相关生长因子三方面的参与，而生长因子作为维持微环境的重要组成部分，对于组织再生起着重要作用［1-2］。人类尼尔样-1型分子（Nel-like molecule-1, NELL-1）基因位于第11号染色体p15.1p15.2，长度约906 kb，包含20个编码外显子。基因编码的分泌蛋白包含810个氨基酸开放阅读框架，其相对分子质量在糖基化之前约为90 000。NELL-1是人类颅缝早闭症相关的一种分泌蛋白，结构包含有6个表皮生长样因子结构域，一个分泌信号肽，一个N末端分子，4个半胱氨酸富集区。NELL-1与胚胎系统发育密切相关，在骨骼系统的发育进程中扮演着重要角色，其具有良好的诱导骨再生与软骨再生的能力，尤其是针对软骨细胞系有较高的特异性。相对于经典的成骨诱导因子骨形态发生蛋白-2（bone morphogenetic protein 2, BMP-2），NELL-1具有特异性强、诱导成骨的骨质更为致密、不良反应小等优势。近年来，NELL-1在组织工程领域进行了大量的研究，NELL-1研究涉及的方面主要包括基因或者蛋白结构及其表达谱［3-4］、生物学功能［5-6］、分子调控机制［7-8］、与疾病相关性［9-10］等。NELL-1与胚胎系统发育密切相关，在骨骼系统的发育进程中扮演着重要角色，其具有良好的诱导骨再生与软骨再生的能力，尤其是针对软骨细胞系有较高的特异性。NELL-1还具有与BMP-2协同作用的能力，NELL-1能够提高细胞对于BMP-2成骨诱导的反应，以及显著降低BMP-2诱发的炎症反应。因此本文拟通过循证医学系统评价的方法综述NELL-1生物学功能。

Regeneration of bone tissue, as well as other tissues, requires involvement and interaction of cells, scaffolds and relevant growth factors, among which growth factors play a crucial role in maintaining the stability of microenvironment. Nel-like-type 1 molecule (NELL-1), a novel growth factor in tissue engineering, has been studied intensively in recent years. Researches mainly covered gene and protein structure and their expression profiling, biological function, molecular mechanisms and disease relevance. NELL-1 expressed in embryonic tissue is essential for growth and development of bone tissue. NELL-1 presents excellent abilities of inducing bone and cartilage regeneration，especially with high specificity to chondrocyte lineage. Compared with classic osteogenic growth factor bone morphogenetic protein 2 (BMP-2）, the process of osteogenesis interacted with NELL-1 exhibits stronger specificity, higher bone density and fewerside effects. Furthermore, a recent study shows synergistic effects of NELL-1 and BMP-2. NELL-1 enhances the osteogenic reaction induced by BMP-2 of cells and notably declines inflammation response caused by BMP-2. This review evaluates the current research progress of the function and application of NELL-1 by the systematic method of evidence-based medicine.