GDF5 MEDIATION OF TENDON HEALING

临床上，生长因子如生长和分化 因子（GDF）代表了肌腱治疗的独特潜力 受伤 为了在临床环境中有效地施用这些药剂， 完全了解它们在肌腱中的作用机制 保养和维修是必不可少的。 作为第一个活体动物 在一个GDF基因的无效突变模型，短足症 小鼠突变体提供了一个独特的实验系统， GDFs在哺乳动物中的作用这项研究的目的是检查 GDF-5对肌腱维持和愈合的作用。 了解 GDF-5的体内作用将使这个生长因子家族能够 考虑用于肌腱修复的治疗用途。 基线 将在短足症中检查跟腱的特征 小鼠，其在GDF-5基因中具有已知的无效突变。 小鼠 具有相同遗传背景但具有两个正常GDF-5等位基因将起作用 作为对照 拟议的实验将提供必要的 短足类动物和对照动物肌腱特性的基线特征 小鼠，以及阐明短期和长期愈合反应， 跟腱损伤。 这些研究结合联合收割机， 了解GDF在肌腱维护中的作用机制 和修复。 在第一组实验中，研究了GDF-5在细胞凋亡中的作用。 建立正常肌腱的生物力学特性， 考察 6周龄跟腱的力学特性 短足类小鼠将从拉伸机械试验中获得， 与对照相比。 为了解释机械性能的差异， 组织学、成分、分子和超微结构 将使用分子生物学的标准技术评估表征。 生物学、生物化学、光学和透射电子显微镜。 在第二组实验中，GDF-5在肌腱修复中的作用 将被审查。跟腱的中间物质切断术将 在6周大的小鼠中进行。 组织学，成分， 分子和超微结构反应将在3， 5、7、9、11、14、28和42天。 钢筋束结构完整性将 分别于术后1、3、5、7、9周行生物力学检查。

Clinically, growth factors such as the growth and differentiation factors (GDFs) represent a unique potential for the treatment of tendon injuries. To administer these agents effectively in a clinical setting, a complete understanding of their mechanisms of action in tendon maintenance and repair is essential. As the first viable in vivo animal model with a null mutation in one of the GDF genes, the brachypodism mouse mutant provides a unique experimental system for examining the role of GDFs in mammals. The goal of this research is to examine the effects of GDF-5 on tendon maintenance and healing. Understanding the in vivo role of GDF-5 will allow this family of growth factors to be considered for therapeutic use in tendon repair. Baseline characterization of Achilles tendon will be examined in the brachypodism mouse, which has a known null mutation in the gene for GDF-5. Mice with the same genetic background but with two normal GDF-5 alleles will serve as controls. The proposed experiments will provide the necessary baseline characterization of tendon properties in brachypod and control mice, as well as elucidate the short and long-term healing response to Achilles tendon injury. These studies combine to enhance our understanding of the mechanisms of action of GDFs in tendon maintenance and repair. In the first set of experiments, the role of GDF-5 in the establishment of normal tendon biomechanical properties will be examined. Mechanical properties of Achilles tendons from 6-week-old brachypod mice will be obtained from tensile mechanical tests and compared to controls. To explain differences in mechanical properties, histologic, compositional, molecular and ultrastructural characterization will be assessed using standard techniques of molecular biology, biochemistry, and light and transmission electron microscopy. In the second set of experiments, the role of GDF-5 in tendon repair will be examined. Mid-substance tenotomies of the Achilles tendon will be created in 6-week-old mice. The histologic, compositional, molecular, and ultrastructural response will be characterized after 3, 5, 7, 9, 11, 14, 28, and 42 days. Tendon structural integrity will be examined biomechanically at 1, 3, 5, 7, and 9 weeks after tenotomy.