组织器官再生与结构功能重构障碍的机制研究为组织再生研究奠定重要的理论基础。在衰老、糖尿病病理状态下，炎症因子、糖基化终末产物增多，氧化应激增强等是已知导致骨代谢障碍、抑制骨再生的重要原因。本项目通过复杂性状遗传小鼠和人群单核苷酸多态性基因分析发现TXNIP是调控骨代谢和再生的重要蛋白；明确TXNIP在衰老、糖尿病时表达显著增高；构建成骨、破骨细胞TXNIP条件和全身敲除小鼠均为骨量升高表型；探索发现TXNIP与ECD相互作用调控糖代谢，进而影响成骨破骨细胞功能。因此提出假说：衰老和糖尿病病理状态下异常升高的TXNIP与ECD直接作用，调控成骨、破骨细胞内的糖代谢进而抑制骨代谢和骨再生。研究将通过阐明TXNIP-ECD复合物的结构与功能来明确氧化应激与糖代谢信号通路的交互机制，在此基础上分析该通路交互对成骨破骨细胞功能的调控作用，为干预TXNIP-ECD复合物来治疗骨再生的策略提供理论依据。

To understand the underlying molecular mechanisms that regulate tissue regeneration is important for future tissue regeneration. It is well known that aging and diabetes are detrimental for bone regeneration due to elevated imflammatory factors, ROS and acumulated advanced glycosylated endproducts. We have previously analysis a serious of gene mining mice and identified TXNIP as an important gene that can regulate bone homeostasis. More importantly, we found the snp in TXNIP is also positively correlated with bone mineral density in human. In addition, we found that TXNIP is upregulated during aging as well as diabetes. Therefore, we generated osteoblast, osteoclast specific knockout out TXNIP and global TXNIP knockout mice. We found these mice all exhibited high bone mass phenotype. We further demonstrated that TXNIP knockout disrupted glycolysis and therefore ostoeblast and osteoclast function. To furhter understand the mechanisms, we identified TXNIP interacts with ECD, a protein that is important for glycolysis. Therefore, we hypothesized that TXNIP-ECD interaction is important for glcolysis in osteoblast and osteoclast, therefore affect the bone regeneration during aging and diabetes. In this study, we will further clarify the structure and function of TXNIP-ECD complex to understand the mechanism of oxidation-glucose metabolism signaling pathway interaction. We will also explore the regulatory role of this signaling pathway on osteoblast and osteoclast function for providing a theoretical basis of potential strategies that treating bone regeneration through intervening TXNIP-ECD complex.