The role of NELL-1, a growth factor associated with craniosynostosis, in promoting bone regeneration.
The role of NELL-1, a growth factor associated with craniosynostosis, in promoting bone regeneration.
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DOI：
10.1177/0022034510376401
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发表时间：
2010-09
影响因子：
7.6
通讯作者：
Soo C
中科院分区：
文献类型：
--
作者：
Zhang X;Zara J;Siu RK;Ting K;Soo C
在过去的十年里，随着再生医学的日益成熟，在骨科和牙科病例中增强骨再生的努力稳步增长。为了满足对新型骨特异性生长因子的前所未有的需求，与现有的骨形成蛋白（BMP）相比，这种生长因子的不良反应更少，我们的研究小组已经确定了一种颅缝早闭相关的分泌分子NELL-1，这是一种对骨软骨细胞谱系高度特异的强效生长因子，并且已经在从啮齿动物到临床前大型动物的多种体内模型中证明了对骨的稳健诱导。NELL-1在Runx 2的直接转录控制下优先在成骨细胞中表达，并且在骨骼发育过程中受到良好调控。NELL-1/Nell-1可以通过膜内或软骨内骨化促进颅面复合体内外的原位骨再生。与BMP-2不同，Nell-1不能启动肌肉中的异位骨形成，但可以诱导骨髓基质细胞（BMSC）在小鼠肌袋模型中形成骨，表现出BMP缺乏的特异性。此外，已经观察到Nell-1和BMP组合疗法的协同成骨作用，并且可能是由于它们的信号传导途径的明显差异。NELL-1作为一种新的骨诱导生长因子的独特作用使其成为一种有吸引力的替代品，具有未来临床应用的前景。[Note：NELL-1和NELL-1分别表示人基因和蛋白质; Nell-1和Nell-1分别表示小鼠基因和蛋白质。]
Efforts to enhance bone regeneration in orthopedic and dental cases have grown steadily for the past decade, in line with increasingly sophisticated regenerative medicine. To meet the unprecedented demand for novel osteospecific growth factors with fewer adverse effects compared with those of existing adjuncts such as BMPs, our group has identified a craniosynostosis-associated secreted molecule, NELL-1, which is a potent growth factor that is highly specific to the osteochondral lineage, and has demonstrated robust induction of bone in multiple in vivo models from rodents to pre-clinical large animals. NELL-1 is preferentially expressed in osteoblasts under direct transcriptional control of Runx2, and is well-regulated during skeletal development. NELL-1/Nell-1 can promote orthotopic bone regeneration via either intramembranous or endochondral ossification, both within and outside of the craniofacial complex. Unlike BMP-2, Nell-1 cannot initiate ectopic bone formation in muscle, but can induce bone marrow stromal cells (BMSCs) to form bone in a mouse muscle pouch model, exhibiting specificity that BMPs lack. In addition, synergistic osteogenic effects of Nell-1 and BMP combotherapy have been observed, and are likely due to distinct differences in their signaling pathways. NELL-1's unique role as a novel osteoinductive growth factor makes it an attractive alternative with promise for future clinical applications. [Note: NELL-1 and NELL-1 indicate the human gene and protein, respectively; Nell-1 and Nell-1 indicate the mouse gene and protein, respectively.]
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