NELL-1：高效特异的新型生长因子

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。

NELL-1:a novel highly efficient and specific growth factor

SUMMARY Regenerationofbonetissue,aswellasothertissues,requiresinvolvementandinteraction of cells,scaffolds and relevant growth factors,among which growth factors play a crucial role in maintai-ning the stability of microenvironment.Nel-like-type 1 molecule (NELL-1 ),a novel growth factor in tis-sue engineering,has been studied intensively in recent years.Researches mainly covered gene and pro-tein structure and their expression profiling,biological function,molecular mechanisms and disease rele-vance.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 spe-cificity to chondrocyte lineage.Compared with classic osteogenic growth factor bone morphogenetic pro-tein 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 in-flammation 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.