氧化应激状态下PPARγ介导RANKL/RANK/OPG调控成骨/破骨对基于xTDM-aDFCSs构建生物牙根影响的相关研究

组织工程器官有效解决器官移植供体来源有限难题，但植入物免疫源性、移植创伤等均诱发宿主发生持续氧化应激直接影响植入物存活，导致移植失败。生物牙根与宿主有效结合是成/破骨对生物牙根与颌骨协同改建最终结果。作为成/破骨调控关键，RANKL/RANK/OPG在氧化应激状态下如何对生物牙根再生发挥作用？项目组已发现PPARγ通过诱导M2巨噬细胞替代激活有效调控宿主免疫排斥，但对RANKL/RANK/OPG影响及可能机制如何？这些瓶颈亟待解决。本项目拟在前期采用猕猴牙缺失模型基于xTDM-aDFCSs成功构建生物牙根基础上，利用氧化应激模型鼠研究氧化应激对牙根发育影响，探索氧化应激状态下PPARγ介导RANKL/RANK/OPG调控成/破骨对生物牙根及其周围骨组织协同再生影响及可能机制，优化牙根再生策略，为生物牙根构建及其临床应用奠定理论及生物技术基础，为利用组织工程器官解决人类重大疾病治疗提供借鉴。

Tissue engineering is one of the most effective means to solve the problem of limited donors in organ grafting. But hosts’ oxidative stress induced by immunogenicity, graft injury and other aspects affects directly to survival rates of grafts, which leads to failure.The effective combination of bio root and hosts is the final result of the coordinated remodeling of bio-root and jaws through the balance between the osteogenesis/osteoclastogenesis. It is unknown that how does RANKL/RANK/OPG as the key element, coordinate the balance between the osteogenesis/osteoclastogenesis. Our group has demonstrated that PPARγ regulates immunological rejection effectively through inducing M2 macrophage alternative activation. It is urgently to be figured out the effects and regulation mechanisms of RANKL/RANK/OPG to the osteogenesis/osteoclastogenesis. Based on successful bio-root construction from xTDM-aDFCSs on rhesus monkey model, our group plan to explore effects of oxidative stress to tooth root development using oxidative stress model mice. We want to explore the effects and mechanisms of the regulation of RANKL/RANK/OPG to the balance between osteogenesis/osteoclastogenesis to bio-root, which aims to optimize bio root regeneration. This can lay a theoretical and practical foundation for construction and clinical application of bio-root as well as offer as a reference for utilizing tissue engineering organs to find therapies for human major diseases.