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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Heterotopic ossification of degenerating rat skeletal muscle induced by adenovirus-mediated transfer of bone morphogenetic protein-2 gene.
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Heterotopic ossification of degenerating rat skeletal muscle induced by adenovirus-mediated transfer of bone morphogenetic protein-2 gene.

机译：腺病毒介导的骨形态发生蛋白2基因转移引起的变性大鼠骨骼肌异位骨化。

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摘要

In vivo gene transfer is a recently developed device for efficient delivery of a therapeutic recombinant protein. We formulated the hypothesis that a high level of expression of bone morphogenetic protein 2 (BMP-2) could be a future therapeutic modality in terms of inducing substantial bone formation in vivo. First, to test this hypothesis, adenoviruses carrying BMP-2 gene were directly injected into the soleus muscle of adult rat. The BMP-2 gene was successfully overexpressed in the target muscle by adenovirus-mediated transfer, whereas bone formation in and around the muscle failed to occur in this case. Second, to recruit putative osteoprogenitor cells, we then induced ischemic degeneration of the target muscle by orthotopically grafting it simultaneously with the gene transfer. The combination of BMP-2 gene transfer and orthotopic muscle grafting resulted in successful ossification of almost the whole grafted muscle, whereas neither muscle grafting alone nor the combination of muscle grafting and adenovirus-mediated transfer of reporter gene LacZ induced any bone formation in the muscle. The ossification process was evident by positive von Kossa staining of the histological sections and roentgenographical radio-opacity of the region. It was also found that the BMP-2 transgene overexpressed in grafted muscles inhibited muscle regeneration, which should otherwise follow the muscle degeneration. We further demonstrated an up-regulation of BMP receptor type IA in grafted muscles, suggesting its involvement in the bone-formation process. In conclusion, overexpression of BMP-2 gene induced massive heterotopic ossification in skeletal muscles under graft-induced ischemic degeneration, which possibly up-regulates osteoprogenitor cells in situ.
机译：体内基因转移是最近开发的用于有效递送治疗性重组蛋白的装置。我们提出了这样的假设：就诱导体内大量骨形成而言，骨形态发生蛋白2（BMP-2）的高表达可能是未来的治疗方式。首先，为了验证这一假设，将带有BMP-2基因的腺病毒直接注射到成年大鼠的比目鱼肌中。 BMP-2基因通过腺病毒介导的转移成功地在靶肌肉中过表达，而在这种情况下，在肌肉内和周围的骨形成未能发生。其次，为了募集推定的骨祖细胞，我们通过与基因转移同时进行原位移植来诱导靶肌肉的缺血性变性。 BMP-2基因转移与原位肌肉移植相结合可导致几乎整个移植的肌肉成功骨化，而单独的肌肉移植或肌肉移植与腺病毒介导的报告基因LacZ的转移均不会诱导肌肉中的任何骨形成。骨化过程通过组织切片的阳性von Kossa染色和该区域的X线放射线不透性而明显可见。还发现，在移植的肌肉中过表达的BMP-2转基因抑制了肌肉的再生，否则肌肉再生就应该随之而来。我们进一步证明了移植肌肉中IA型BMP受体的上调，表明其参与了骨形成过程。总之，在移植物诱导的缺血性变性下，BMP-2基因的过表达诱导骨骼肌大量异位骨化，这可能在原位上调了骨祖细胞。

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