摘要
背景:在脊柱融合术中进行充分植骨是非常必要的,然而,老龄患者自身成骨细胞数量有限和骨微环境改变以及骨形态发生蛋白2体内应用会引起例如异位骨等不利影响,导致目前的治疗方法会引起骨不连和其他并发症。在此情况下,Nel样分子1型(Nel-like type 1 molecular,Nell-1)进入研究人员的视野,Nell-1不仅在成骨活性上与骨形态发生蛋白2相当,而且具有抗脂肪、抗炎、促血管化的特性,这为Nell-1促进脊柱融合的临床试验批准奠定了基础。目的:综述Nell-1促进脊柱融合术后骨性融合中的作用及机制。方法:由第一作者检索百度学术、PubMed、Web of Science、万方及中国知网收录的相关文献,中文检索词为“Nell-1、脊柱融合、骨性融合、前成骨细胞分化、新生血管、祖细胞迁移”,英文检索词为“Nell-1;spinal fusion;bone fusion;pre-osteoblast differentiation;neovascularization;progenitor cell migration”,最后纳入68篇文献进行综述。结果与结论:自体骨移植存在植骨相关并发症以及来源不足等问题,而且以骨形态发生蛋白2为代表的骨移植替代治疗会产生许多非靶点效应,因此两者都不能满足日益增加的脊柱融合术的需求。在此背景下,Nell-1的出现为解决这种困境提供了可能。虽然Nell-1在脊柱融合术后促进骨性融合的作用还处于初级研究阶段,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,但其具有促进祖细胞迁移、前成骨细胞分化以及新生血管形成等特点,因此对于促进脊柱融合术后骨性融合具有巨大的潜力。未来的研究应进一步揭示详细的潜在机制、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,将Nell-1促进脊柱融合的潜力转化为临床实践。
BACKGROUND:Adequate bone grafting is very necessary during spinal fusion.However,due to the limited number of osteoblasts and the function of the bone microenvironment in elderly patients,as well as the in vivo application of bone morphogenetic protein 2 will cause adverse effects such as ectopic bone.The current method can cause nonunion and other complications.In this case,Nel-like molecule-1(Nell-1)has entered the field of vision of researchers.Nell-1 is not only equivalent to BMP-2 in osteogenic activity,but also has anti-fat,anti-inflammatory,and pro-vascular properties.These laid the foundation for clinical trial approval of Nell-1 in promoting spinal fusion.OBJECTIVE:To review the effect and mechanism of Nell-1 on bone fusion after spinal fusion.METHODS:Relevant documents were retrieved in Baidu Academic,PubMed,Web of Science,Wanfang,and CNKI.The Chinese and the English search terms were“Nell-1,spinal fusion,bone fusion,pre-osteoblast differentiation,neovascularization,progenitor cell migration”.Finally,68 articles were included for review.RESULTS AND CONCLUSION:Autologous bone grafting has complications and supply problems related to bone grafting.Bone graft replacement therapy represented by bone morphogenetic protein 2 will produce many non-target effects.Therefore,neither can meet the increasing demand for spinal fusion.In this context,the emergence of Nell-1 provides the possibility to solve this dilemma.Although the role of Nell-1 in promoting bone fusion after spinal fusion is still in the preliminary stage of research,there are still deficiencies in the lack of an optimal route of administration;the molecular mechanism is not fully understood;and whether there are adverse reactions related to the application.Nevertheless,it has the triple effect of promoting progenitor cell migration,pre-osteoblast differentiation,and vascularization,so it has great potential for promoting bone fusion after spinal fusion.Future research should further reveal the detailed underlying mechanism,optimize the dosage
作者
唐小凯
李伟明
Tang Xiaokai;Li Weiming(Harbin Medical University,Harbin 150001,Heilongjiang Province,China;Department of Orthopedics,First Affiliated Hospital of Harbin Medical University,Harbin 150001,Heilongjiang Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2021年第24期3914-3920,共7页
Chinese Journal of Tissue Engineering Research
基金
中国博士后科学基金项目(2016M601449),项目负责人:李伟明。
