Gene therapy:: Adenovirus-mediated human bone morphogenetic protein-2 gene transfer induces mesenchymal progenitor cell proliferation and differentiation in vitro and bone formation in vivo
Gene therapy:: Adenovirus-mediated human bone morphogenetic protein-2 gene transfer induces mesenchymal progenitor cell proliferation and differentiation in vitro and bone formation in vivo
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DOI：
10.1002/jor.1100170108
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发表时间：
1999-01-01
影响因子：
2.8
通讯作者：
Manske, P
中科院分区：
文献类型：
--
作者：
Lou, JR;Xu, F;Manske, P
本研究报告重组腺病毒介导的人骨形态发生蛋白-2基因转移可以诱导间充质祖细胞分化和骨形成。构建携带人骨形成蛋白-2基因的重组腺病毒，并通过特异性抗体检测腺病毒介导的成熟人骨形成蛋白-2表达。在腺病毒介导的骨形态发生蛋白基因转移下，间充质祖细胞系C3 H/10 T 1/2显示细胞增殖依赖于腺病毒骨形态发生蛋白剂量。经腺病毒骨形态发生蛋白转导的C3 H/10 T1/2细胞也表现出向成骨细胞表型的分化，这表明碱性磷酸酶活性。将C3 H/10 T1/2细胞注射到裸鼠大腿肌肉中，在X线片上可检测到小骨的发育。组织学分析表明，在小鼠大腿肌肉中发育的新的小骨具有不同的骨成分，包括骨小梁、骨髓和骨化组织。本研究的结果表明，通过腺病毒介导的骨形态发生蛋白基因转移的基因治疗的潜力。
This study reports that recombinant adenovirus-mediated human bone morphogenetic protein-2 gene transfer can induce mesenchymal progenitor cell differentiation and bone formation. The recombinant adenovirus with the human bone morphogenetic protein-2 gene was constructed, and mature human bone morphogenetic protein-2 expression mediated by adenovirus gene transfer was detected by specific antibody. Under adenovirus-mediated bone morphogenetic-protein gene transfer, mesenchymal progenitor cell line C3H/10T 1/2 showed cell proliferation dependent on adenovirus bone morphogenetic-protein dose. The C3H/10T 1/2 cells transduced by adenovirus bone morphogenetic protein also exhibited differentiation to osteoblast phenotype, which indicates alkaline phosphatase activity. Injection of the C3H/10T 1/2 cells into the thigh muscles of nude mice led to ossicle development detectable on radiographs, Histological analysis indicated that the new ossicles that developed in the thigh muscles of the mice had different osseous components including bone trabeculae, bone marrow, and chondrified tissue. The results of this study demonstrate the potential for gene therapy by adenovirus-mediated bone morphogenetic-protein gene transfer.