Controlled Release of Bone Morphogenetic Protein-2 Enhances Recruitment of Osteogenic Progenitor Cells for De Novo Generation of Bone Tissue

Controlled Release of Bone Morphogenetic Protein-2 Enhances Recruitment of Osteogenic Progenitor Cells for De Novo Generation of Bone Tissue
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DOI:
10.1089/ten.tea.2009.0322
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发表时间:
2010-04-01
影响因子:
4.1
通讯作者:
Tabata, Yasuhiko
Tabata, Yasuhiko
中科院分区:
医学3区
文献类型:
--
作者:
Kimura, Yu;Miyazaki, Nobuhiko;Tabata, Yasuhiko

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本研究的目的是评估细胞对骨形态发生蛋白 2 (BMP-2) 受控释放诱导的骨组织从头生成现象的贡献。将掺有不同含水量的 BMP-2(3 mg)的明胶水凝胶(2 mg)皮下植入增强型绿色荧光蛋白嵌合小鼠背部,诱导骨组织异位从头生成。掺入 BMP-2 的水凝胶可以在不同的时间曲线上释放 BMP-2。当进行放射学和组织学评估时,骨组织的异位从头生成是由水凝胶植入部位周围的水凝胶受控释放 BMP-2 诱导的。招募到从头生成的骨组织中的绿色荧光蛋白与骨钙素阳性细胞的相对百分比数量取决于 BMP-2 释放曲线。百分比越高,骨组织的从头生成越强。这些发现表明,通过 BMP-2 的释放,从血液循环中招募骨髓来源的成骨细胞祖细胞,从而促进骨组织的异位从头生成。可以想象,BMP-2 的局部浓度改变了 BMP-2 释放位点周围具有成骨潜力的祖细胞的募集情况,从而调节了从头生成的骨组织的体积。
The objective of this study was to evaluate the cellular contribution to the phenomenon of de novo generation of bone tissue induced by the controlled release of bone morphogenetic protein-2 (BMP-2). Gelatin hydrogels (2 mg) incorporating BMP-2 ( 3 mg) with different water contents were subcutaneously implanted into the back of enhanced green fluorescent protein-chimeric mice to induce the ectopic de novo generation of bone tissue. The hydrogels incorporating BMP-2 could release BMP-2 at different time profiles. When evaluated radiologically and histologically, the ectopic de novo generation of bone tissue was induced by the controlled release of BMP-2 from the hydrogels around the hydrogel-implanted site. The relative percentage number of green fluorescent protein- to osteocalcin-positive cells recruited into the de novo generated bone tissue depended on the BMP-2 release profile. The higher the percentage, the stronger was the de novo generation of bone tissue. These findings indicate that bone marrow-derived osteoblast progenitor cells were recruited from the blood circulation by BMP-2 release and consequently contributed to the ectopic de novo generation of bone tissue. It is conceivable that the local concentration of BMP-2 modifies the recruitment profile of progenitor cells with an osteogenic potential around the release site of BMP-2, resulting in regulated volume of de novo generated bone tissue.