肥胖和骨质疏松二者密切相关，调控体内脂肪形成与骨形成之间的平衡可能有助于这两种疾病的治疗。脂肪形成与骨形成之间的平衡对骨量和骨内环境稳态的维持也至关重要。骨髓间充质干细胞（BMSCs）具有向脂肪和成骨细胞分化的潜能，调控其分化方向是治疗骨质疏松的新靶标。DEPTOR是mTOR的内源性抑制因子。DEPTOR可调控干细胞分化及体内脂肪形成，而其是否调控BMSCs分化及体内脂肪形成与骨形成之间的平衡却尚不清楚。课题组前期研究发现DEPTOR可调控BMSCs向成骨细胞或脂肪细胞分化的定向，还可能参与调控体内脂肪形成与骨形成之间的平衡，但相关机制有待进一步研究。本项目拟构建全身敲除和BMSCs特异性敲除DEPTOR的小鼠、细胞以及肥胖和骨质疏松的小鼠模型，多层次研究DEPTOR在调控BMSCs分化及体内脂肪形成与骨形成平衡中的作用及相关机制，以期为肥胖与骨质疏松的的防治提供理论支撑。

Obesity and osteoporosis are closely related. Treatment of the two diseases depends on the balance lipogenesis and bone formation. Moreover, maintenance of bone mass and homeostasis also relies on coordinated adipogenesis and osteogenesis. Bone marrow mesenchymal stem cells (BMSCs) has the potential to differentiate into adipocytes and osteoblasts, and the differentiation directions of BMSCs has emerged as a new target for osteoporosis treatment. As an endogenous inhibitory factor of mTOR, DEPTOR has been reported to regulate stem cell differentiation, while its role in BMSCs differentiation is unclear. DEPTOR also has been reported to participate in the regulation of body fat formation, its role in the balance between adipogenesis and bone formation in the body, however, awaits further investigation. Our previous data showed that DEPTOR exerted essential roles in determining the differentiation of BMSCs into osteoblasts or adipocytes, and may be involved in regulating the balance between adipogenesis and bone formation in the body, while the responsible mechanisms remain to be further studied. In the present study, we intend to construct mouse models with DEPTOR knockout in the whole body and specifically in BMSCs and with disease of obesity and osteoporosis, so as to investigate the role of DEPTOR in differentiation of BMSCs and in the balance between lipogenesis and bone formation in the body and provide theoretical support for the prevention and treatment of obesity and osteoporosis.