Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant morbidity.The differentiation of mesenchymal stem cells into the osteogenic l...Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant morbidity.The differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth factors.Neural EGF Like-Like molecule 1(NELL-1)is a secreted glycoprotein that has proven,both in vitro and in vivo,to be a potent osteo-inductive factor.Furthermore,it has been shown to repress adipogenic differentiation and inflammation.NELL-1 can work synergistically with other osteogenic factors such as Bone Morphogenic Protein(BMP)2 and9,and has shown promise for use in tissue engineering and as a systemically administered drug for the treatment of osteoporosis.Here we provide a comprehensive up-to-date review on the molecular signaling cascade of NELL-1 in mesenchymal stem cells and potential applications in bone regenerative engineering.展开更多
Nel样1型分子基因(Nel-like type 1 molecule gene,Nell-1)作为一种新型基因定位于染色体11p15.1-p15.2。目前的研究表明Nell-1基因编码的外分泌型糖蛋白(Nell-1蛋白)可作为骨生长因子,诱导成骨细胞分化成熟与矿化、抑制脂滴的形成及炎...Nel样1型分子基因(Nel-like type 1 molecule gene,Nell-1)作为一种新型基因定位于染色体11p15.1-p15.2。目前的研究表明Nell-1基因编码的外分泌型糖蛋白(Nell-1蛋白)可作为骨生长因子,诱导成骨细胞分化成熟与矿化、抑制脂滴的形成及炎症反应等,因此临床上作为颅面部缺损及骨质疏松症等疾病的治疗,在骨组织工程中发挥重要作用。近期研究发现Nell-1蛋白阳性还可以用来定义一种新型原发性膜性肾病,为膜性肾病的诊断提供新的理论依据。本文就Nell-1基因的发现与结构、Nell-1蛋白的结构、功能及表达、作用机制及临床应用方面展开讨论,并对目前关于Nell-1的最新研究及展望进行小结。展开更多
基金Research in the authors’laboratories was supported in part by research grants from the National Institutes of Health(AT004418,DE020140 to TCH and RRR)the US Department of Defense(OR130096 to JMW)+4 种基金the Scoliosis Research Society(TCH and MJL)the 973 Program of the Ministry of Science and Technology(MOST)of China(#2011CB707906 to TCH)MP and SM were recipients of the Pritzker Summer Research Fellowship funded through the National Institute of Health(NIH)T-35 training grant(NIDDK)#T35DK062719-30The reported work was also supported in part by The University of Chicago Cancer Center Support Grant(P30CA014599)the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430。
文摘Bone tissue regeneration holds the potential to solve both osteoporosis and large skeletal defects,two problems associated with significant morbidity.The differentiation of mesenchymal stem cells into the osteogenic lineage requires a specific microenvironment and certain osteogenic growth factors.Neural EGF Like-Like molecule 1(NELL-1)is a secreted glycoprotein that has proven,both in vitro and in vivo,to be a potent osteo-inductive factor.Furthermore,it has been shown to repress adipogenic differentiation and inflammation.NELL-1 can work synergistically with other osteogenic factors such as Bone Morphogenic Protein(BMP)2 and9,and has shown promise for use in tissue engineering and as a systemically administered drug for the treatment of osteoporosis.Here we provide a comprehensive up-to-date review on the molecular signaling cascade of NELL-1 in mesenchymal stem cells and potential applications in bone regenerative engineering.
文摘Nel样1型分子基因(Nel-like type 1 molecule gene,Nell-1)作为一种新型基因定位于染色体11p15.1-p15.2。目前的研究表明Nell-1基因编码的外分泌型糖蛋白(Nell-1蛋白)可作为骨生长因子,诱导成骨细胞分化成熟与矿化、抑制脂滴的形成及炎症反应等,因此临床上作为颅面部缺损及骨质疏松症等疾病的治疗,在骨组织工程中发挥重要作用。近期研究发现Nell-1蛋白阳性还可以用来定义一种新型原发性膜性肾病,为膜性肾病的诊断提供新的理论依据。本文就Nell-1基因的发现与结构、Nell-1蛋白的结构、功能及表达、作用机制及临床应用方面展开讨论,并对目前关于Nell-1的最新研究及展望进行小结。
