Aghaloo Tara, Cowan Catherine M, Zhang Xinli, Freymiller Earl, Soo Chia, Wu Benjamin, Ting Kang, Zhang Zhiyuan
Dental and Craniofacial Research Institute and Section of Oral and Maxillofacial Surgery, School of Dentistry, University of California, Los Angeles, CA, USA.
J Oral Maxillofac Surg. 2010 Feb;68(2):300-8. doi: 10.1016/j.joms.2009.03.066.
Most craniofacial birth defects contain skeletal components that require bone grafting. Although many growth factors have shown potential for use in bone regeneration, bone morphogenetic proteins (BMPs) are the most osteoinductive. However, supraphysiologic doses, high cost, and potential adverse effects stimulate clinicians and researchers to identify complementary molecules that allow a reduction in dose of BMP-2. Because NELL1 plays a key role as a regulator of craniofacial skeletal morphogenesis, especially in committed chondrogenic and osteogenic differentiation, and a previous synergistic mechanism has been identified, NELL1 is an ideal molecule for combination with BMP-2 in calvarial defect regeneration. We investigated the effect of NELL1 and BMP-2 on bone regeneration in vivo.
BMP-2 doses of 589 and 1,178 ng were grafted into 5-mm critical-sized rat calvarial defects, as compared with 589 ng of NELL1 plus 589 ng of BMP-2 and 1,178 ng of NELL1 plus 1,178 ng of BMP-2, and bone regeneration was analyzed.
Live micro-computed tomography data showed increased bone formation throughout 4 to 8 weeks in all groups but a significant improvement when the lower doses of each molecule were combined. High-resolution micro-computed tomography and histology showed more mature and complete defect healing when the combination of NELL1 plus BMP-2 was compared with BMP-2 alone at lower doses.
The observed potential synergy has significant value in the future treatment of patients with craniofacial defects requiring extensive bone grafting that would normally entail extraoral autogenous bone grafts or doses of BMP-2 in milligrams.
大多数颅面先天性缺陷包含需要骨移植的骨骼成分。尽管许多生长因子已显示出用于骨再生的潜力，但骨形态发生蛋白（BMP）是最具骨诱导性的。然而，超生理剂量、高成本和潜在的不良反应促使临床医生和研究人员寻找能够减少BMP - 2剂量的互补分子。由于NELL1作为颅面骨骼形态发生的调节因子发挥关键作用，特别是在定向软骨生成和成骨分化中，并且先前已确定了协同机制，因此NELL1是与BMP - 2联合用于颅骨缺损再生的理想分子。我们研究了NELL1和BMP - 2对体内骨再生的影响。
将589 ng和1178 ng的BMP - 2植入5毫米临界大小的大鼠颅骨缺损中，与之相比，还植入589 ng的NELL1加589 ng的BMP - 2以及1178 ng的NELL1加1178 ng的BMP - 2，并分析骨再生情况。
活体微型计算机断层扫描数据显示，所有组在4至8周内骨形成均增加，但当将每种分子的较低剂量联合使用时，有显著改善。高分辨率微型计算机断层扫描和组织学显示，与单独使用较低剂量的BMP - 2相比，NELL1加BMP - 2联合使用时缺损愈合更成熟、更完整。
观察到的潜在协同作用在未来治疗需要广泛骨移植的颅面缺损患者中具有重要价值，这类患者通常需要进行口外自体骨移植或使用毫克级剂量的BMP - 2。
