Alcohol-Induced Oxidative Stress and MSC Differentiation During Fracture Repair

骨折修复过程中酒精诱导的氧化应激和 MSC 分化

• 批准号: 9556968
• 负责人: JOHN J. CALLACI
• 金额: $ 17.93万
• 依托单位: LOYOLA UNIVERSITY CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-05 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9556968
• 关键词: Accidents; Admission activity; Adolescent and Young Adult; Affect; Aging; Alcohol abuse; Alcohol consumption; Alcohols; Animals; Antioxidants; Area; Attenuated; Beverages; Bone Transplantation; Bone callus; Bone necrosis; Cell Lineage; Chondrocytes; Clinical; Complication; Country; Data; Development; Diabetes Mellitus; Disease; Early Promoters; Exposure to; FOXO1A gene; Fracture; Fracture Healing; Free Radicals; Goals; Heavy Drinking; Hospitals; In Vitro; Injury; Inpatients; Investigation; Laboratories; LacZ Genes; Life; Mesenchymal Stem Cells; Minerals; Molecular; Morbidity - disease rate; Operative Surgical Procedures; Organ; Orthopedics; Osteoblasts; Osteogenesis; Oxidative Stress; Patients; Pattern; Persons; Phosphorylation; Population; Preparation; Process; Public Health; Rattus; Reactive Oxygen Species; Reporter; Research; Risk; Rodent; Serine; Signal Transduction; Site; Skeleton; Stem cells; Therapeutic; Time; Tissues; Transgenic Organisms; Trauma patient; Traumatic injury; United States; WNT Signaling Pathway; alcohol effect; alcohol exposure; base; binge drinking; bone; cartilaginous; cellular targeting; drinking behavior; experimental study; fetal; healing; improved; in vivo; injured; mortality; negative affect; novel; osteogenic; outcome forecast; problem drinker; regenerative; repaired; self-renewal; skeletal injury; stem cell differentiation; stem cell technology; 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 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.

7.项目总结/摘要 过量饮酒导致疾病和增加创伤性损伤的风险 严重影响了美国的公共卫生负担。骨骼是一个重要的目标器官， 酒精的有害影响，因为它以两种不同的方式遭受酒精相关的损害;两者都直接来自 过量饮酒，间接由于酒精引起的创伤性损伤的风险增加 饮酒行为骨折不愈合是骨折损伤不能正常愈合的情况，需要 手术干预和饮酒已被证明有助于这种严重的临床风险 并发症目前，对于患有不愈合骨折的患者的临床选择，例如手术移植 自体或脱矿骨制备物各自具有严重的局限性。获取自体骨 移植物实际上是一种单独的外科手术，存在另一组并发症和脱矿骨的风险 准备工作不可靠。正常的骨折愈合是一个再生过程，利用干细胞重建 伤口处有新的骨头然而，我们目前并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， 成功修复骨折这项调查的目的是了解酒精是否会影响 骨髓间充质干细胞向软骨细胞分化的实验研究 MSC向软骨细胞分化的减少可能是酒精相关的骨折骨痂抑制的基础 形成和骨折愈合因为年轻人更容易遭受创伤性伤害， 了解间歇性饮酒或酗酒对骨折修复的影响，因为酗酒是 青少年和年轻成年人饮酒的流行模式。事实上，大约40% 的骨科住院患者在入院时醉酒， 了解酗酒对骨折修复过程的影响的重要性。我们 我相信从这项提案中获得的数据将有助于更好地了解酒精的原因 消耗对骨折修复过程产生负面影响，以及我们如何改善 骨科创伤合并骨折损伤患者合并饮酒 通过使用干细胞技术。

项目成果

Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro.

• DOI: 10.1186/s13018-018-0800-7
• 发表时间: 2018-04-27
• 期刊: Journal of orthopaedic surgery and research
• 影响因子: 2.6
• 作者: Natoli RM;Yu H;Meislin MC;Abbasnia P;Roper P;Vuchkovska A;Xiao X;Stock SR;Callaci JJ
• 通讯作者: Callaci JJ

The Effect of Proton Pump Inhibitors on Bone Formation in a Rat Spinal Arthrodesis Model.

质子泵抑制剂对大鼠脊柱关节固定模型中骨形成的影响。

• DOI: 10.1097/brs.0000000000002987
• 发表时间: 2019
• 期刊: Spine
• 影响因子: 3
• 作者: Sonn,KevinA;Wallace,StephenJ;Yuan,FengNingF;Schneider,AndrewD;Hsu,ErinL;Havey,RobertM;Patwardhan,AvinashG;Callaci,JohnJ
• 通讯作者: Callaci,JohnJ

Effects of Episodic Alcohol Exposure on BMP2 Signaling During Tibia Fracture Healing.

• DOI: 10.1097/bot.0000000000001160
• 发表时间: 2018-06
• 期刊: Journal of orthopaedic trauma
• 影响因子: 2.3
• 作者: Bratton A;Eisenberg J;Vuchkovska A;Roper P;Callaci JJ
• 通讯作者: Callaci JJ

Impact of Alcohol on Bone Health, Homeostasis and Fracture repair.

• DOI: 10.1007/s40139-020-00209-7
• 发表时间: 2020-09
• 期刊: Current pathobiology reports
• 作者: Eby JM;Sharieh F;Callaci JJ
• 通讯作者: Callaci JJ