Stimulation of new bone formation by direct transfer of osteogenic plasmid genes
Stimulation of new bone formation by direct transfer of osteogenic plasmid genes
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DOI：
10.1073/pnas.93.12.5753
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发表时间：
1996-06-11
影响因子：
11.1
通讯作者：
Roessler, BJ
中科院分区：
文献类型：
--
作者：
Fang, JM;Zhu, YY;Roessler, BJ
将含有表达质粒DNA的可降解基质[基因激活基质（GAM）]植入成年大鼠股骨中产生的节段间隙中。植入含有β-半乳糖苷酶或荧光素酶质粒的GAM导致生长到差距中的修复细胞（肉芽组织）摄取DNA并表达功能性酶。植入含有骨形态发生蛋白-4质粒或编码甲状旁腺激素片段（氨基酸1-34）的质粒的GAM导致新骨填充差距的生物学反应。最后，植入一个双质粒GAM编码骨形态发生蛋白-II和甲状旁腺激素片段，在体外协同作用，导致新骨形成速度比单独使用任何一种因子。这些研究首次证明，骨中的修复细胞（成纤维细胞）可以在体内进行遗传操作。在作为研究修复成纤维细胞和伤口愈合反应的生物学的有用工具的同时，GAM技术也可能具有广泛的治疗用途。
Degradable matrices containing expression plasmid DNA [gene-activated matrices (GAMs)] were implanted into segmental gaps created in the adult rat femur. Implantation of GAMs containing beta-galactosidase or luciferase plasmids led to DNA uptake and functional enzyme expression by repair cells (granulation tissue) growing into the gap. Implantation of a GAM containing either a bone morphogenetic protein-4 plasmid or a plasmid coding for a fragment of parathyroid hormone (amino acids 1-34) resulted in a biological response of new bone filling the gap. Finally, implantation of a two-plasmid GAM encoding bone morphogenetic protein-ii and the parathyroid hormone fragment, which act synergistically in vitro, caused new bone to form faster than with either factor alone. These studies demonstrate for the first time that repair cells (fibroblasts) in bone can be genetically manipulated in vivo. While serving as a useful tool to study the biology of repair fibroblasts and the wound healing response, the GAM technology may also have wide therapeutic utility.