The role of muscle cells in bone repair

骨愈合的失败导致显著的疼痛和残疾，使得骨折修复的增强是一个动态和重要的研究领域。在我们希望引入新的成功疗法之前，对骨修复的充分理解是必要的。我们相信，对参与骨愈合的细胞起源的更好理解可能会导致新的手术，药物和细胞为基础的治疗方法来治疗骨质疏松症的骨修复。已知来源于骨髓和骨膜的干细胞分化成成熟骨细胞并产生骨。然而，在许多严重的开放性骨折中，这些组织受损或难以接近骨损伤部位。在这些情况下，骨修复通常在邻近对侧肌肉的区域开始。这使我们推测，来自肌肉的细胞可能直接有助于骨修复。已发表的研究，已被我们的小组证实，已经证明了肌源性祖细胞（卫星细胞）在响应骨形态发生蛋白等刺激时成为骨样细胞的强大潜力。为了正确看待肌细胞的成骨潜力，我们计划扩展这些研究，并将小鼠卫星细胞与小鼠骨髓干细胞进行比较。此外，我们计划使用一种转基因小鼠，其肌肉细胞永久性地遗传转化为蓝色。这种小鼠将使我们能够评估肌细胞的命运及其对异位骨形成和骨折修复模型中骨形成的贡献。本研究将在最基本的水平上探索肌肉对骨修复的细胞贡献。这项研究项目的结果将显着影响我们的治疗方向，以改善骨折修复在未来。

Failure of bone healing leads to significant pain and disability, such that augmentation of fracture repair is a dynamic and important field of study. A full understanding of bone repair is necessary before we can hope to introduce novel successful therapies. We believe that a improved understanding of the origins of the cells involved with bone healing may lead to new surgical, drug and cell-based therapies for the treatment of recalcitrant bone repair. Stem cells originating from the bone marrow and periosteum are known to differentiate into mature bone cells and produce bone. However, these tissues are damaged or have poor access to the site of bone injury in many severe open fractures. In these cases, bone repair often initiates in a region adjacent to an opposing muscle. This has led us to speculate that cells from the muscle may directly contribute to bone repair. Published studies, which have be confirmed by our group, have demonstrated the strong potential for muscle-derived progenitor cells (satellite cells) to become bone-like in response to stimuli such as bone morphogenic proteins. To put bone-forming potential of muscle cells in perspective, we plan to expand on these studies and compare mouse satellite cells with mouse bone marrow stem cells. In addition, we plan to use a transgenic mouse whose muscle cells become permanently genetically transformed to stain blue. This mouse will allow us to assess the fate of muscle cells and their contribution to bone formation in ectopic bone formation and fracture repair models. This study will explore on the most basic level the cellular contribution of muscle to bone repair. The results of this research project will significantly influence our therapeutic directions for improving fracture repair in the future.