NAMPT regulation of fracture tissue metabolism during bone healing

NAMPT 对骨愈合过程中骨折组织代谢的调节

• 批准号: 10700625
• 负责人: Charles Rundle
• 金额: --
• 依托单位: VA LOMA LINDA HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10700625
• 关键词: Adenosine; Age; Aging; Agonist; Anabolism; Animal Model; Blood Vessels; Bone Density; Bone callus; Cartilage; Cell Proliferation; Cell physiology; Chronic; Clinical; Clinical Pathology; Complications of Diabetes Mellitus; Data; Development; Diabetes Mellitus; Diabetic mouse; Dinucleoside Phosphates; Dose; Economics; Fracture; Future; General Population; Health; High Fat Diet; Histologic; Histology; Immunohistochemistry; Impairment; In Vitro; Inflammation; Injury; Intervention; Longevity; Measurement; Measures; Mediator; Medical; Metabolic; Metabolism; Mus; NADH; Niacinamide; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oryctolagus cuniculus; Osteoclasts; Osteogenesis; Overweight; Oxidation-Reduction; Pathologic; Pathway interactions; Periosteal Cell; Physiological; Population; Prevalence; Probability; Process; Production; Radiology Specialty; Reactive Oxygen Species; Regulation; Roentgen Rays; Safety; Signal Pathway; Testing; Therapeutic; Therapeutic Intervention; Tibial Fractures; Time; Tissues; Titrations; Type 2 diabetic; United States; Veterans; Wild Type Mouse; antagonist; bone; bone cell; bone fracture repair; bone healing; bone repair; cell motility; comorbidity; dosage; efficacy testing; healing; immune cell infiltrate; improved; in vivo; microCT; mouse model; nicotinamide phosphoribosyltransferase; novel; novel strategies; novel therapeutic intervention; patient population; pharmacologic; repaired; response; sensor; skeletal; small molecule; therapeutic candidate; tissue repair; wound; wound healing

This proposal will optimize NAD functions in the metabolism of fracture tissues for the enhancement of bone fracture repair in an obesity/Type-2 diabetic condition, a condition that is common in the general population and even more frequent among veterans. It is well established that Type-2 diabetics suffer from impaired bone healing caused by an insufficient metabolic response to the requirements of tissue repair. In this study, an obesity/Type-2 diabetes condition will be induced in mice and the redox potential of local tissues improved through the augmentation of NAMPT functions in the fracture tissues. Selected agonists of NAMPT will be screened for their effects in periosteal cells, therapeutic candidates locally applied to the fracture tissues in obesity/Type-2 diabetic mice and fracture healing evaluated. The completion of the proposed studies should facilitate the development of novel therapeutic interventions that improve tissue responses to the metabolic requirements of wound repair.

该建议将优化断裂组织代谢中的NAD功能，以增强 肥胖/2型糖尿病状况下的骨断裂修复 在退伍军人中，人口甚至更频繁。众所周知，2型糖尿病患者患有 由于对组织修复需求的代谢反应不足而导致的骨骼愈合受损。在 这项研究，将在小鼠中诱导肥胖/2型糖尿病状况和局部氧化还原电位 通过碎裂组织中NAMPT功能的增加而改善组织。选定的激动剂 NAMPT将筛选其在骨膜细胞中的作用，当地应用的治疗候选者 评估了肥胖/2型糖尿病小鼠的骨折组织和骨折愈合。完成 拟议的研究应促进新的治疗干预措施的发展 对伤口修复的代谢要求的反应。