The role of muscle cells in bone repair

骨愈合失败会导致严重的疼痛和残疾，因此增强骨折修复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，对骨修复的充分了解是必要的。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，药物和基于细胞的疗法来治疗顽固性骨修复。来源于骨髓和骨膜的干细胞可以分化成成熟的骨细胞并生成骨。然而，在许多严重的开放性骨折中，这些组织受损或难以进入骨损伤部位。在这种情况下，骨修复通常始于对跖肌附近的区域。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，已经被我们的小组证实，已经证明了肌肉来源的祖细胞（卫星细胞）在响应诸如骨形态形成蛋白的刺激时具有强大的潜力，成为骨样细胞。为了更好地了解肌肉细胞的成骨潜力，我们计划在这些研究基础上进行扩展，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老鼠，它的肌肉细胞被永久地遗传转化为蓝色。这只小鼠将使我们能够评估肌肉细胞的命运及其在异位骨形成和骨折修复模型中对骨形成的贡献。本研究将从最基本的层面探讨肌肉细胞对骨修复的贡献。本课题的研究结果将对我们今后提高骨折修复的治疗方向产生重要影响。

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.