2005 Fiscal Year Final Research Report Summary
Analysis of roles for osteopontin in muscle regeneration
| Project/Area Number |
16590333
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National Institute of Nueroscience, NCNP |
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Principal Investigator |
SUZUKI Yuko National Institute of Neuroscience, NCNP, Department of Molecular Therapy, Section Chief, 遺伝子疾患治療研究部, 室長 (00342931)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Shinichi National Institute of Neuroscience, NCNP, Department of Molecular Therapy, Director, 遺伝子疾患治療研究部, 部長 (90171644)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Skeletal muscle / muscle regeneration / satellite cells / cytokine / osteopontin / mesenchymal stem cells / macrophage / Side population cells |
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| Research Abstract |
First, we examined muscle regeneration of osteopontin-null mice. Contrary to our expectation, osteopontin-null muscle successfully regenerated after cardiotoxin injection. To further examine the molecular and cellular regulation of muscle regeneration, we next examined a novel cell population in skeletal muscle : side population cells. Although skeletal muscle regeneration has been exclusively attributed to myogenic precursors, satellite cells, a stem cell-rich fraction referred to as side population (SP) cells also resides in skeletal muscle, and are proposed to play an important role in muscle regeneration. To further clarify the function of SP cells in muscle regeneration, we isolated this cell population from normal and regenerating muscle by cell sorter, and found that muscle SP cells are heterogeneous : they could be subdivided into three cell populations using CD31 and CD45 markers. The majority of SP cells in normal muscle expressed CD31 and had endothelial characteristics. CD31^-CD45^- SP cells, which are a minor fraction in normal conditions, actively proliferated upon muscle injury, and expressed not only several regulatory genes for muscle regeneration but also some mesenchymal lineage markers. CD31^-CD45^- SP cells showed the greatest myogenic potential among three SP sub-fractions, and differentiated to adipocytes, chondrocytes, or myotubes in vitro. In vivo, these SP cells preferentially differentiated into myofibers after intramuscular transplantation. They also promote muscle regeneration when transplanted into 5-FU-treated muscle together with myoblasts. Our results suggest that CD31^-CD45^- SP cells are mesenchymal stem cell-like cells and play important roles in muscle regeneration.
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