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IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors.

Sacco A, Doyonnas R, LaBarge MA, Hammer MM, Kraft P, Blau HM - J. Cell Biol. (2005)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology, Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.

ABSTRACT
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.

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DNA electrotransfer of IGF-I increases the contribution of BMDCs to skeletal muscle. (a) The two muscle-specific isoforms, IGF-IEa and MGF, are shown to be up-regulated in the muscle after notexin damage as shown by RT-PCR analysis. (b) Plasmids encoding IGF-IEa.CD8, MGF.CD8, or CD8 only (control) were electroporated into the TA muscles of mice that had received a BMT 8 wk earlier, and muscles were harvested 4 wk after DNA delivery. The percentage of GFP+CD8+ myofibers relative to total CD8+ myofibers is shown (± SEM). P value was determined with a t test. *, P < 0.02. (c) Immunofluorescence images of transverse sections of muscle stained for CD8 only (left) or for GFP and CD8 (right). GFP+ cells <10 μm are blood cells. Arrows indicate examples of CD8+ myofibers that were also GFP+. Bars, 50 μm.
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fig1: DNA electrotransfer of IGF-I increases the contribution of BMDCs to skeletal muscle. (a) The two muscle-specific isoforms, IGF-IEa and MGF, are shown to be up-regulated in the muscle after notexin damage as shown by RT-PCR analysis. (b) Plasmids encoding IGF-IEa.CD8, MGF.CD8, or CD8 only (control) were electroporated into the TA muscles of mice that had received a BMT 8 wk earlier, and muscles were harvested 4 wk after DNA delivery. The percentage of GFP+CD8+ myofibers relative to total CD8+ myofibers is shown (± SEM). P value was determined with a t test. *, P < 0.02. (c) Immunofluorescence images of transverse sections of muscle stained for CD8 only (left) or for GFP and CD8 (right). GFP+ cells <10 μm are blood cells. Arrows indicate examples of CD8+ myofibers that were also GFP+. Bars, 50 μm.

Mentions: The two muscle-specific IGF-I isoforms IGF-IEa and MGF were selected for study. Both isoforms were previously reported to be up-regulated upon muscle damage (Hill and Goldspink, 2003). To confirm that this was the case, mouse skeletal muscle tissues were injected with notexin, a potent inducer of muscle damage (Harris et al., 1974; Pluskal et al., 1978; Klein-Ogus and Harris, 1983). RT-PCR analysis of total RNA from muscle revealed an increase in IGF-IEa and MGF transcripts 8 d after injury (Fig. 1 a).


IGF-I increases bone marrow contribution to adult skeletal muscle and enhances the fusion of myelomonocytic precursors.

Sacco A, Doyonnas R, LaBarge MA, Hammer MM, Kraft P, Blau HM - J. Cell Biol. (2005)

DNA electrotransfer of IGF-I increases the contribution of BMDCs to skeletal muscle. (a) The two muscle-specific isoforms, IGF-IEa and MGF, are shown to be up-regulated in the muscle after notexin damage as shown by RT-PCR analysis. (b) Plasmids encoding IGF-IEa.CD8, MGF.CD8, or CD8 only (control) were electroporated into the TA muscles of mice that had received a BMT 8 wk earlier, and muscles were harvested 4 wk after DNA delivery. The percentage of GFP+CD8+ myofibers relative to total CD8+ myofibers is shown (± SEM). P value was determined with a t test. *, P < 0.02. (c) Immunofluorescence images of transverse sections of muscle stained for CD8 only (left) or for GFP and CD8 (right). GFP+ cells <10 μm are blood cells. Arrows indicate examples of CD8+ myofibers that were also GFP+. Bars, 50 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171272&req=5

fig1: DNA electrotransfer of IGF-I increases the contribution of BMDCs to skeletal muscle. (a) The two muscle-specific isoforms, IGF-IEa and MGF, are shown to be up-regulated in the muscle after notexin damage as shown by RT-PCR analysis. (b) Plasmids encoding IGF-IEa.CD8, MGF.CD8, or CD8 only (control) were electroporated into the TA muscles of mice that had received a BMT 8 wk earlier, and muscles were harvested 4 wk after DNA delivery. The percentage of GFP+CD8+ myofibers relative to total CD8+ myofibers is shown (± SEM). P value was determined with a t test. *, P < 0.02. (c) Immunofluorescence images of transverse sections of muscle stained for CD8 only (left) or for GFP and CD8 (right). GFP+ cells <10 μm are blood cells. Arrows indicate examples of CD8+ myofibers that were also GFP+. Bars, 50 μm.
Mentions: The two muscle-specific IGF-I isoforms IGF-IEa and MGF were selected for study. Both isoforms were previously reported to be up-regulated upon muscle damage (Hill and Goldspink, 2003). To confirm that this was the case, mouse skeletal muscle tissues were injected with notexin, a potent inducer of muscle damage (Harris et al., 1974; Pluskal et al., 1978; Klein-Ogus and Harris, 1983). RT-PCR analysis of total RNA from muscle revealed an increase in IGF-IEa and MGF transcripts 8 d after injury (Fig. 1 a).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Pharmacology, Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus