骨质疏松是危害严重的全球性公共卫生问题。研究表明，雌激素缺乏导致的骨重建失衡是绝经后骨质疏松的主要原因，但具体机制仍未明确。. 外泌体是一种活细胞分泌的纳米级囊泡，介导细胞间的信息传递和功能调控。最新研究表明，骨细胞来源的外泌体在全身性骨重建调节中发挥重要功能，其作用受多种外部因素的影响。我们前期发现，雌激素诱导下，成骨细胞外泌体表达量和蛋白质构成发生显著变化。进一步研究显示，其内含的整合素系统（Integrin α1β1、α6β1）及其相关蛋白表达升高，推测可能是雌激素调控骨重建平衡的关键环节，但其作用特性和分子调控网络亟待进一步阐明。据此，我们设计本课题，拟利用定量蛋白质组学平台结合基因编辑技术，进一步分析和验证雌激素介导成骨细胞外泌体整合素系统、调控骨重建的作用和相关分子机制，以期深刻认识绝经后骨质疏松的病理生理变化，为骨质疏松治疗提供新的思路及治疗靶点。

Osteoporosis is a serious global public health problem. The postmenopausal osteoporosis is closely related to the disequilibrium of bone remodeling, which results from the estrogen deficiency. However, its regulatory mechanism has been largely unknown. . Exosome is a newly discovered vesicle communicator, which is involved in the signal transduction and regulation of cell function. It is proved to be influenced by many external factors stimulation. Recent studies have shown that osteoblasts can achieve systemic bone remodeling regulation through exosomes. Our previous work found that estrogen can affect the secretion and protein composition of exosomes of osteoblasts, and may identify the important cells involved in bone remodeling through the integrin system (Integrin α1β1, α6β1) in them, then activate the downstream signaling pathway to maintaining balance of bone remodeling. While the precise recognition characteristic and molecular regulation network needs to be further elucidated. Thus, we designed the comprehensive project involves quantitative proteomics and bioinformatics research platform in combination with genome-editing technique to further analyze the roles and molecular mechanisms of estrogen-mediated exosome integrins of osteoblasts in regulation of bone remodeling.