脂肪因子在骨骼形成中发挥重要的作用，如leptin，adiponectin等，新的脂肪因子chemerin既可以调节骨髓间充质干细胞向成骨方向分化，又可以调控造血干细胞向破骨细胞分化，表明chemerin与骨形成有关。然而，作为chemerin的功能性受体之一，CMKLR1，所介导的通路在骨形成中的作用至今没有详尽的报道。我们前期研究结果发现雄性CMKLR1 基因敲除小鼠体内睾酮含量明显偏低并且骨密度明显减少，提示CMKLR1与睾酮合成相关，且与睾酮相关的骨形成有关。本项目在体内水平通过建立雄性小鼠骨质疏松模型研究CMKLR1对小鼠骨质量的影响以及雄激素相关的骨合成作用；在体外水平培养睾丸间质细胞、骨髓间充质干细胞和破骨细胞，研究CMKLR1对睾丸间质细胞合成睾酮、骨髓间充质干细胞成脂/成骨分化、成骨-破骨细胞稳态平衡的影响，阐明CMKLR1信号在雄激素合成异常引起骨质疏松中的作用机制。

Adipokines play an important role in bone formation, such as leptin, adiponectin. New adipokine chemerin can regulate osteogenic differentiation of bone marrow mesenchymal stem cells, and they also regulate hematopoietic stem cells into osteoclast differentiation, suggesting that chemerin associated with bone formation. However, as one of the chemerin’s functional receptors, CMKLR1, the effect in bone formation has been no report. Our preliminary study found that CMKLR1 KO male mice had significantly lower testosterone and decreasing bone mineral density than WT mice, suggesting that CMKLR1 associated with testosterone synthesis and bone formation. We will study the effects of CMKLR1 on bone mass in mice and androgen-related bone formation in vivo by male osteoporosis mice model; and the mechanism of bone metabolism by cultured Leydig cells, bone marrow mesenchymal stem cells and osteoclasts in vitro, clarify the role of CMKLR1 signal in osteoporosis by abnormal androgen synthesis.