间充质干细胞（mesenchymal stem cells，MSCs）是一类具有自我更新和分化潜能的成体干细胞。利用MSCs分化为成骨细胞治疗骨质疏松是目前研究的热点和难点。我们前期发现 AJUBA被Smad1调控，AJUBA敲除小鼠骨量丢失,向成骨细胞分化能力减弱，RNA-seq发现STAT5和Runx2的表达下调，STAT5的磷酸化被抑制。我们提出科学假说：AJUBA通过激活STAT5的磷酸化及入核，上调Runx2等下游基因的表达，促进MSCs向成骨细胞分化。本课题将研究：1、明确AJUBA激活STAT5/Runx2信号通路促进MSC向成骨细胞分化的命运决定；2、阐明AJUBA在MSCs被BMP-Smad1调控的分子机制；3、探讨AJUBA作为诱导MSCs分化成骨细胞治疗骨质疏松的可行性。对以上问题的回答，期望完善MSCs分化成骨细胞的分子机制，为骨质疏松的预防和治疗提供可能性与策略。

Mesenchymal stem cells (MSCs) are a class of adult stem cells with self-renewal and differentiation potential. The use of MSCs to differentiate into osteoblasts for the treatment of osteoporosis is a hot and difficult point in current research. Previously, AJUBA was regulated by Smad1, AJUBA knockout mice were found to lose bone mass and weaken their ability to differentiate into osteoblasts. RNA-Seq was found to down-regulate the expression of STAT5 and Runx2, and phosphorylation of STAT5 was inhibited. Based on the above research, a scientific hypothesis was proposed: AJUBA activates STAT5 Phosphorylation and nuclear import, up-regulation of Runx2 and other downstream gene expression, and promotion of MSC differentiation into osteoblasts. In this project: 1. We would identify AJUBA's activation of STAT5/Runx2 signaling pathway to promote the fate of MSC to osteoblast differentiation; 2. We would elucidate the molecular mechanism of AJUBA in the regulation of MSCs by BMP-Smad1; 3. We would explore the feasibility of AJUBA as an induced MSC differentiation into osteoblasts for the treatment of osteoporosis, the answer to the above questions, it is expected that the perfect MSC differentiation into osteoblasts. The molecular mechanism provides possibilities and strategies for the prevention and treatment of osteoporosis.