IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors
IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors
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DOI：
10.1083/jcb.200506123
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发表时间：
2005-11-07
影响因子：
7.8
通讯作者：
Blau, HM
中科院分区：
文献类型：
--
作者：
Sacco, A;Doyonnas, R;Blau, HM
肌肉损伤可以增强骨髓来源的细胞(BMDCs)在再生骨骼肌中的作用。参与这一过程的一种负责细胞类型是一种造血干细胞衍生物，即粒单核细胞前体(MMC)。然而，负责这种与伤害相关的反应的分子成分在很大程度上仍不清楚。在这篇文章中，我们证明了通过三种不同的方法将胰岛素样生长因子-I(IGF-I)输送到成人骨骼肌--电穿孔、基因工程成肌细胞注射和重组蛋白注射--使BMDCs的整合增加四倍。为了探讨其潜在的机制，我们开发了一种体外融合实验，将MMCs和肌管共培养的细胞暴露于IGF-I。IGF-I显著增加了融合事件的数量，与其对细胞存活的影响无关。这些结果提供了新的证据，表明单一的IGF-I因子足以促进骨髓衍生品与成人骨骼肌的融合。
Muscle damage has been shown to enhance the contribution of bone marrow - derived cells ( BMDCs) to regenerating skeletal muscle. One responsible cell type involved in this process is a hematopoietic stem cell derivative, the myelomonocytic precursor (MMC). However, the molecular components responsible for this injury-related response remain largely unknown. In this paper, we show that delivery of insulin-like growth factor I (IGF-I) to adult skeletal muscle by three different methods - plasmid electroporation, injection of genetically engineered myoblasts, and recombinant protein injection - increases the integration of BMDCs up to fourfold. To investigate the underlying mechanism, we developed an in vitro fusion assay in which co-cultures of MMCs and myotubes were exposed to IGF-I. The number of fusion events was substantially augmented by IGF-I, independent of its effect on cell survival. These results provide novel evidence that a single factor, IGF-I, is sufficient to enhance the fusion of bone marrow derivatives with adult skeletal muscle.