近年骨骼作为一个内分泌器官调控能量代谢的观点已被广泛接受。本课题组前期研究发现全身性LGR4敲除的小鼠(LGR4m/m)出现体重降低，抵抗肥胖的能量代谢表型，主要由白色脂肪棕色化引起，但脂肪前体细胞LGR4敲除并不能完全解释脂肪前体细胞向棕色脂肪细胞的分化。本课题组初步发现成骨细胞（OB）特异性敲除LGR4的小鼠（LGR4osb-/-）出现能量代谢表型跟LGR4m/m小鼠类似，并且发现由OB特异性分泌的并促进白色脂肪棕色化的SOST水平升高，因此我们推测OB的LGR4可能参与了能量代谢的调控，并通过调节SOST表达实现。本研究将利用LGR4osb-/-小鼠，体外慢病毒敲除OB的LGR4等方法探讨成骨细胞的LGR4对能量代谢的调控，并深入探讨成骨细胞LGR4通过调节SOST表达而调控能量代谢及机制，明确骨质疏松、肥胖等代谢性疾病发病机制中的共同通路，并为这些疾病的防治提供新的靶点。

In recent years, bone has been widely accepted as an endocrine organ to regulate energy metabolism. Our previous study found the increasing energy-consuming and obesity-resistance phenotype of the global LGR4 knok-out（LGR4m/m）mice mainly due to browning of white adipose tissue, LGR4 knockdown of adipose precursor cells does not fully explain the differentiation of adipose precursor cells toward brown-like adipocytes. Our group initially found that mice with osteoblast-specific knockout (LGR4osb-/-) showed an energy metabolism phenotype similar to that of global knockout mice, and SOST levels that promote browning of white fat and is secreted specifically by osteocytes increased. Thus osteoblastic LGR4 may be involved in the regulation of energy metabolism by regulating SOST. With the use of LGR4osb-/- mice，LGR4 knock-down lentivirus in osteoblast and so on，we aim to explore regulation and mechanism of osteogenic LGR4 on energy metabolism by regulating SOST expression. This project shed light on illustrating the common pathway in the pathogenesis of osteoporosis and obesity and thus discovering new target in prevention and treatment of these diseases.