NAMPT regulation of fracture tissue metabolism during bone healing

该建议将优化NAD在骨折组织代谢中的功能，以增强 肥胖症/2型糖尿病状况中的骨折修复， 在退伍军人中更常见。众所周知，2型糖尿病患者患有 由于对组织修复要求的代谢反应不足而导致的骨愈合受损。在 在这项研究中，将在小鼠中诱导肥胖症/2型糖尿病病症，并且局部的氧化还原电位将被降低。 通过增强骨折组织中的NAMPT功能来改善组织。选择的激动剂 NAMPT将筛选其在骨膜细胞中的作用，治疗候选物局部应用于 在肥胖/2型糖尿病小鼠中的骨折组织和评估的骨折愈合。的完成 拟议的研究应有助于开发新的治疗干预措施， 对伤口修复的代谢需求的反应。

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.