Role of muscle-derived growth factors in bone formation.
Role of muscle-derived growth factors in bone formation.
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DOI：
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发表时间：
2010-03
影响因子：
1.9
通讯作者：
Mark W. Hamrick;Paul L. McNeil;Stella L. Patterson
中科院分区：
文献类型：
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作者：
Mark W. Hamrick;Paul L. McNeil;Stella L. Patterson
肌肉和骨骼的附着和附着在生长、发育和衰老过程中是紧密耦合的，然而连接这两种组织的细胞和分子机制还没有很好地理解。在这里，我们表明，FGF-2和IGF-1，两个生长因子已知在调节骨形成中发挥重要作用，是本地化的肌纤维沿着的肌肉-骨界面的小鼠前肢。同样地，这些生长因子的受体也丰富地存在于沿着长骨骨干的肌肉附着处附近的骨膜中。从均质化的小鼠前肢肌肉中定量生长因子水平，发现IGF-1是最丰富的因子，还检测到FGF-2。还分析了来自培养的肌管的条件培养基中的生长因子水平，并且再次检测到显著水平的IGF-1和FGF-2。机械损伤C2 C12肌管增加FGF-2释放到条件培养基中，而IGF-1分泌的浓度低于FGF-2损伤后。总之，这些发现表明，肌肉是骨组织生长因子的重要局部来源。因此，骨和肌肉的整合生长和发育可能部分受肌肉-骨界面处的旁分泌机制调节，所述旁分泌机制涉及生长因子信号传导。
Muscle and bone anabolism and catabolism are tightly coupled during growth, development, and aging, yet the cellular and molecular mechanisms linking these two tissues are not well understood. Here we show that FGF-2 and IGF-1, two growth factors known to play a major role in regulating bone formation, are localized to muscle fibers along the muscle-bone interface of the mouse forelimb. Likewise, receptors for these growth factors are also abundant in periosteum adjacent to fleshy muscle attachments along the diaphysis of long bones. Growth factor levels were quantified from homogenized mouse forelimb muscles and IGF-1 was found to be the most abundant factor with FGF-2 also detected. Growth factor levels were also analyzed in conditioned medium from cultured myotubes, and IGF-1 and FGF-2 were again detected at significant levels. Mechanically wounding C2C12 myotubes increased the release of FGF-2 into conditioned medium, whereas IGF-1 was secreted at lower concentrations than FGF-2 following injury. Together these findings suggest that muscle is an important, local source of growth factors for bone tissue. Hence, the integrated growth and development of bone and muscle is likely to be regulated in part by paracrine mechanisms at the muscle-bone interface involving growth factor signaling.