Nell-1 enhances bone regeneration in a rat critical-sized femoral segmental defect model.
Nell-1 enhances bone regeneration in a rat critical-sized femoral segmental defect model.
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NELL-1增强了大鼠临界股股节段缺陷模型中的骨再生。
DOI：
10.1097/prs.0b013e3181fed5ae
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发表时间：
2011-02
影响因子：
3.6
通讯作者：
Soo C
中科院分区：
文献类型：
--
作者：
Li W;Zara JN;Siu RK;Lee M;Aghaloo T;Zhang X;Wu BM;Gertzman AA;Ting K;Soo C
在骨科、牙科和颅面重建中，有效的骨再生对于骨折修复和骨移植的并入和愈合至关重要。Nell-1(NEL样分子-1)是从颅缝融合患者的颅缝中发现的一种分泌蛋白，已被发现特异性地刺激成骨细胞分化和骨形成。为了测试Nell-1在体内的成骨能力，采用了一种临界大小的大鼠股骨节段性缺损模型。在每只大鼠的左侧股骨中都产生了一个6毫米长的缺陷，如果不进行治疗，可能会导致骨不连。设1.5 mg/mlNell-1组、0.6 mg/mlNell-1组和PBS对照组，每组8例。植入前将PBS或Nell-1与脱钙骨基质混合作为载体。所有动物在术后12周被安乐死，并通过放射学、三维显微CT和组织学分析评价骨再生。与无Nell-1组相比，Nell-1处理的两个剂量组的骨形成显著增加，骨体积随着Nell-1浓度的增加而增加。脱钙骨基质载体中的Nell-1可显著促进临界大小的股骨节段缺损处的骨再生，并呈剂量依赖关系。本研究结果表明，Nell-1是一种有效的骨特异性生长因子，值得进一步研究。结果还支持Nell-1作为骨移植替代品的潜在应用，在多种临床场景中，当自体移植骨有限或不可用时，涉及修复关键的骨丢失。
Effective regeneration of bone is critical for fracture repair and incorporation and healing of bone grafts used during orthopedic, dental, and craniofacial reconstructions. Nell-1 (Nel-like molecule-1) is a secreted protein identified from prematurely fused cranial sutures of craniosynostosis patients that has been found to specifically stimulate osteogenic cell differentiation and bone formation. To test the in vivo osteoinductive capacity of Nell-1, a critical-sized femoral segmental defect model in athymic rats was used. A 6-mm defect, which predictably leads to non-union if left untreated, was created in the left femur of each rat. Three treatment groups (n=8 each) were created consisting of 1.5 mg/ml Nell-1, 0.6 mg/ml Nell-1, and PBS only as a Nell-free control. PBS or Nell-1 were mixed with demineralized bone matrix as carrier prior to implantation. All animals were euthanized 12 weeks post surgery, and bone regeneration was evaluated using radiographic, three-dimensional microCT, and histological analysis. Both doses of Nell-1 treated groups had significantly greater bone formation compared to the Nell-free group, with bone volume increasing with increasing Nell-1 concentration. Nell-1 in a demineralized bone matrix carrier can significantly improve bone regeneration in a critical-sized femoral segmental defect in a dose-dependent manner. The results of this study demonstrate that Nell-1 is a potent osteospecific growth factor that warrants further investigation. Results also support the potential application of Nell-1 as a bone graft substitute in multiple clinical scenarios involving repair of critical bone loss when autograft bone is limited or unavailable.