Alcohol-Induced Oxidative Stress and MSC Differentiation During Fracture Repair

7.项目摘要/摘要 过量饮酒导致疾病并增加创伤伤害的风险 严重加重了美国的公共卫生负担。骨骼是一个重要的靶器官 酒精的有害影响，因为它以两种截然不同的方式遭受与酒精有关的损害；这两种方式都直接来自 过量饮酒，间接原因是酒精造成创伤的风险增加 饮酒行为。骨折不愈合是指骨折损伤无法正常愈合的情况，需要 手术干预和饮酒已被证明是导致这种严重临床风险的原因之一。 很复杂。目前，对于未愈合的骨折患者的临床选择，如手术植骨 自体或去矿化骨制剂都有严重的局限性。自体骨的获取 移植实际上是一种单独的外科手术，面临另一组并发症和脱矿化骨的风险。 准备工作不可靠。正常的骨折愈合是一个利用干细胞重建的再生过程。 伤处有新骨形成。然而，我们目前还不清楚酒精是如何影响干细胞活性的。 骨折部位的细胞。我们认为饮酒对干细胞活性有负面影响，而干细胞活性是至关重要的。 为成功修复骨折干杯。这项调查的目的是了解酒精是否会影响 骨折损伤后间充质干细胞向软骨细胞分化 MSC向软骨细胞分化减少可能是酒精抑制骨折骨痂的原因 形成和骨折愈合。因为年轻人更容易遭受创伤，所以这一点很重要 要了解间歇性饮酒或酗酒对骨折修复的影响，因为酗酒是 青少年和青壮年人群中普遍存在的饮酒模式。约40%的人 骨科住院患者在入院时醉酒的比例强调了 了解酗酒对骨折修复过程的影响的意义。我们 相信从这项提案中获得的数据将有助于更好地理解为什么饮酒 消耗对骨折修复过程产生负面影响，以及我们如何改善 骨科创伤合并骨折伤合并饮酒患者 虽然干细胞技术的使用。

7. PROJECT SUMMARY/ABSTRACT Excessive alcohol consumption resulting in disease and increasing the risk of traumatic injury contributes significantly to the public health burden in the United States. The skeleton is a significant target organ for the deleterious effects of alcohol because it suffers alcohol-related damage in two distinct ways; both directly from excessive alcohol consumption, and indirectly due to the increased risk for traumatic injury caused by alcohol drinking behavior. Fracture nonunion is a condition where a bone fracture injury fails to heal normally requiring surgical intervention and alcohol consumption has been shown to contribute to the risk for this serious clinical complication. Currently, clinical options for patients with a non-healing fracture such as surgical grafting of autogenous or de-mineralized bone preparations each have serious limitations. Obtaining autogenous bone graft is effectively a separate surgical procedure at risk for another set complications and de-mineralized bone preparations are unreliable. Normal fracture healing is a regenerative process that utilizes stem cells to rebuild new bone at the injury site. However, we currently do not understand how alcohol affects the activity of stem cells at the fracture site. We believe that alcohol consumption negatively affects stem cell activity that is critical to successful fracture repair. The goal of this investigation is to understand if alcohol affects mesenchymal stem cell differentiation toward chondrocytes following bone fracture injury and if decreased MSC to chondrocyte differentiation may underlie alcohol related inhibition of fracture callus formation and fracture union. Because young people are more likely to suffer traumatic injury, it is important to understand the effects of episodic or binge drinking on fracture repair as binge alcohol consumption is the prevalent pattern of alcohol drinking in both adolescent and young adult populations. The fact that about 40% of the orthopaedic inpatient population is intoxicated at the time of hospital admission underscores the significance of understanding the impact of binge alcohol consumption on the fracture repair process. We believe that the data obtained from this proposal will lead to a better understanding of why alcohol consumption negatively impacts the fracture repair process and how we can improve the prognosis for orthopaedic trauma patients with bone fracture injuries complicated by concomitant alcohol consumption though the use of stem cell technology.