Effects of Acute and Chronic Alcohol Intoxication on Fracture Healing in Orthopaedic Trauma Patients: Effects on Mesenchymal Stem Cell Lineage Differentiation Required for Fracture Repair

急性和慢性酒精中毒对骨科创伤患者骨折愈合的影响：对骨折修复所需的间充质干细胞谱系分化的影响

• 批准号: 10646469
• 负责人: JOHN J. CALLACI
• 金额: $ 18.29万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-20 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646469
• 关键词: Accidents; Acute; Adolescent and Young Adult; Affect; Alcohol abuse; Alcohol consumption; Alcoholic Intoxication; Alcohols; Area; Beverages; Biological Models; Bone Marrow; Bone Transplantation; Bone callus; Bone necrosis; Caring; Cell Lineage; Cell Separation; Chondrocytes; Chronic; Clinical; Complication; Country; Data; Diabetes Mellitus; Differentiation Antigens; Disease; FOXO1A gene; Fracture; Goals; Heavy Drinking; Histone Deacetylase; Hospitalization; Impairment; Injury; Inpatients; Intervention; Intoxication; Investigation; Laboratories; Life; Mesenchymal Stem Cells; Molecular; Morbidity - disease rate; Operative Surgical Procedures; Organ; Orthopedics; Osteoblasts; Osteogenesis; Pathway interactions; Patients; Pattern; Persons; Physiologic Ossification; Play; Population; Preparation; Process; Productivity; Prognosis; Proteins; Public Health; Regimen; Research; Risk; Risk Factors; Rodent; Rodent Model; Role; Sampling; Signal Transduction; Sirtuins; Site; Skeleton; Smoking; Steroids; Therapeutic; Time; Trauma patient; Traumatic injury; United States; Work; alcohol effect; alcohol exposure; beta catenin; binge drinking; biological adaptation to stress; bone; bone fracture repair; cartilaginous; cell type; clinical effect; clinically relevant; demineralization; drinking behavior; epidemiology study; experimental study; healing; high risk; improved; in vitro Model; in vivo; injured; mortality; negative affect; novel; osteoblast differentiation; osteogenic; pharmacologic; problem drinker; regenerative; skeletal injury; sobriety; stem cell differentiation; stem cell proliferation; stem cells; targeted treatment; treatment strategy

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 exploratory investigation is to examine the effects of alcohol consumption on stem cell differentiation potential, using clinical samples obtained from alcohol-intoxicated orthopaedic trauma patients at the time of surgery. This will be the first examination of whether alcohol consumption at the time of injury affects the ability of stem cells to heal a bone fracture. The study will also examine a potential mechanism that causes alcohol to inhibit stem cells from differentiating into cell types required for normal fracture repair. 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 targeted therapeutic regimens.

7. 项目概要/摘要 过量饮酒会导致疾病并增加外伤风险 严重加重了美国的公共卫生负担。骨骼是重要的靶器官 酒精的有害影响，因为它以两种不同的方式遭受与酒精相关的损害；两者都直接来自 过量饮酒，间接导致酒精造成外伤的风险增加 饮酒行为。骨折不愈合是骨折损伤无法正常愈合的一种情况，需要 手术干预和饮酒已被证明会增加这种严重临床症状的风险 并发症。目前，对于不愈合骨折患者的临床选择，例如手术移植 自体骨或脱矿质骨制剂均具有严重的局限性。获得自体骨 移植实际上是一个单独的外科手术，存在出现另一组并发症和脱矿骨的风险 准备工作不可靠。正常的骨折愈合是利用干细胞重建的再生过程 受伤部位出现新骨。然而，我们目前还不了解酒精如何影响茎的活性 骨折部位的细胞。我们认为饮酒会对干细胞活性产生负面影响，这一点至关重要 才能成功修复骨折。这项探索性调查的目的是检验以下因素的影响： 饮酒对干细胞分化潜力的影响，使用从以下来源获得的临床样本 手术时酒精中毒的骨科创伤患者。这将是第一个 检查受伤时饮酒是否影响干细胞的能力 治愈骨折。该研究还将研究导致酒精抑制的潜在机制 干细胞分化为正常骨折修复所需的细胞类型。因为年轻人 更有可能遭受创伤，了解间歇性或酗酒的影响很重要 酗酒是青少年饮酒的普遍模式 和年轻人口。事实上，大约 40% 的骨科住院患者在 入院时间强调了了解酗酒影响的重要性 骨折修复过程中的消耗。我们相信从该提案中获得的数据将导致 更好地理解为什么饮酒会对骨折修复过程产生负面影响以及我们如何 可以改善骨科创伤并发骨折损伤患者的预后 通过使用有针对性的治疗方案同时饮酒。