CYTOKINES IN FRACTURE HEALING

目前估计约有560万处骨折发生 在美国每年有5%到10%的人 会导致愈合延迟或受损。 虽然生物学 骨折修复已被广泛研究， 过程仍然不完全理解，因此临床问题继续存在 发生。 最近的证据表明，多种细胞间信号和 生长因子参与软组织伤口的愈合 表明这一区域可能代表了我们对骨折知识的空白 修复. 细胞因子是一组免疫调节蛋白，以前被认为是 免疫细胞的独特产物。 从广义上讲：细胞因子是 被认为是一类生长因子。 最近的数据显示， 某些肌肉骨骼组织产生并响应特定的 细胞因子 由于细胞因子调节软组织中的各种细胞事件， 组织伤口愈合，并且由于现在已知这些多肽是 软骨和骨骼中细胞反应的重要修饰剂， 一个项目建议研究特定细胞因子在骨折中的作用 治愈 为一个长期项目奠定基础，阐明如何 特定的细胞因子可以调节骨折愈合的某些方面， 该项目建议采取以下行动： 1. 骨折骨痂器官培养体系的建立及其特性研究 广泛地关于其组织学中的连续变化， 组织形态计量学、生物化学和特定基因的表达 与发育中的愈伤组织有关。 2. 确定特定细胞因子的产生模式， 骨折愈合，并将这些变化与组织学， 组织形态学、生物化学和分子表型变化， 在这个模型中建立起来。 一旦知道骨折产生哪些细胞因子， 在healinq期间，未来的提案可能会被设计为阐明 细胞产生并响应这些多肽，以及它们是如何被调节的 在分子水平上。 最终，有可能开发出 使用细胞因子的治疗，以预防骨折并发症， 治愈 由于各种创伤条件和外科手术需要 骨骼会自我修复， 骨折愈合，从这个项目中获得的知识可以广泛 广泛应用于肌肉骨骼疾病。

It is currently estimated that approximately 5.6 million fractures occur annually in the United States and between five and ten percent of these will result in delayed or impaired healing. Although the biology of fracture repair has been extensively studied several aspects of this process remain incompletely understood and thus clinical problems continue to occur. Recent evidence that a variety of intercellular signals and growth factors are involved in the healing of the soft tissue wounds suggests that this area may represent a gap in our knowledge of fracture repair. Cytokines are a group of immunomodulatory proteins formerly thought to be unique products of immune cells. In the broad sense: cytokines are considered to be a class of growth factors. Recent data indicate that certain musculoskeletal tissues both produce and respond to specific cytokines. Since cytokines regulate a variety of cellular events in soft tissue wound healing, and since these polypeptides are now known to be important modifiers of cellular responses in cartilage and bone, this project proposes to investigate the role of specific cytokines in fracture healing. To lay foundation for a long term project to elucidate how specific cytokines may regulate certain aspects of fracture healing, this project proposes to do the following: 1. Develop a fracture callus organ culture system and characterize it extensively with respect to sequential changes in its histology, histomorphometry, biochemistry and the expression of specific genes associated with developing callus tissues. 2. Determine the pattern of production of Specific cytokines during fracture healing and relate these Changes to the histological, histomorophometric biochemical and molecular phenotypic changes which will have been established in this model. Once it is known which cytokines are produced by fractures and at what times during healinq, future proposals may be designed to elucidate which cells produce and respond to these polypeptides and-how they are regulated at the molecular level. Ultimately, it may be possible to develop therapies using cytokines to prevent fracture complications and enhance healing. Since a variety of traumatic conditions and surgical procedures require that bone repair itself in a fashion similar to that which occurs during fracture healing, the knowledge derived from this project could have wide spread application to musculoskeletal disease.