Synergistic effects of the dual release of stromal cell-derived factor-1 and bone morphogenetic protein-2 from hydrogels on bone regeneration
Synergistic effects of the dual release of stromal cell-derived factor-1 and bone morphogenetic protein-2 from hydrogels on bone regeneration
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DOI：
10.1016/j.biomaterials.2010.12.052
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发表时间：
2011-04-01
期刊：
影响因子：
14
通讯作者：
Tabata, Yasuhiko
中科院分区：
文献类型：
--
作者：
Ratanavaraporn, Juthamas;Furuya, Hiroyuki;Tabata, Yasuhiko
本研究的目的是评价复合基质细胞衍生因子-1(SDF-1)和骨形态发生蛋白-2(BMP-2)的明胶水凝胶对大鼠尺骨临界大小的缺损区和皮下部位的体内骨再生的影响，并与单独使用SDF-1和BMP-2的明胶水凝胶进行比较。在BMP-2和SDF-1联合作用下，SDF-1和BMP-2在水凝胶中的释放规律相似。观察到复合SDF-1和BMP-2的水凝胶促进了骨再生。此外，结合SDF-1和BMP-2的水凝胶植入后，CXC趋化因子细胞表面受体-4(CXCR4)、Runt相关因子-2(Rurva)和骨钙素基因的表达水平增加。对绿色荧光蛋白(GFP)阳性嵌合体小鼠的实验表明，在含有SDF-1和BMP-2的水凝胶植入部位，促进了骨髓来源细胞的募集，并观察到血管样结构以及CD31和CD34阳性细胞的强烈聚集。此外，还检测到大量CD29和CD44阳性的非造血细胞。结论：SDF-1和BMP-2的联合释放促进了成骨细胞的募集和血管生成，对骨再生具有协同作用。(C)2011爱思唯尔有限公司。保留所有权利。
The objective of this study is to evaluate the activity of gelatin hydrogels incorporating combined stromal cell-derived factor-1 (SDF-1) and bone morphogenetic protein-2 (BMP-2) on the in vivo bone regeneration at an ulna critical-sized defect and subcutaneous site of rats, and compared with that of those incorporating either SDF-1 or BMP-2. The similar release profile of SDF-1 and BMP-2 from the hydrogels was observed with or without the combination of BMP-2 and SDF-1, respectively. An enhanced bone regeneration by the hydrogels incorporating combined SDF-1 and BMP-2 was observed. In addition, the implantation of hydrogels incorporating combined SDF-1 and BMP-2 enhanced the expression level of CXC chemokine cell-surface receptor-4 (Cxcr4), Runt-related factor-2 (Rurva), and Osteocalcin genes. The experiments with green fluorescent protein (GFP)-positive Chimeric mice revealed that the recruitment of bone marrow-derived cells was promoted and a vascular-like structure together with strong accumulation of CD31- and CD34-positive cells was observed at the site of hydrogels incorporating combined SDF-1 and BMP-2 implanted. In addition, a large fraction of CD29- and CD44-positive non-hematopoietic cells was detected. It is concluded that the combined release of SDF-1 and BMP-2 enhanced the recruitment of osteogenic cells and angiogenesis, resulting in the synergistic effect on bone regeneration. (C) 2011 Elsevier Ltd. All rights reserved.