骨骼的内分泌功能在机体自稳态的调节中受到越来越多的关注。尽管骨钙素的能量调节作用得到越来越多的证实，最近的研究也发现，成骨细胞中存在着非骨钙素依赖的糖代谢调控机制。本课题通过筛选发现，胰岛再生源蛋白-3γ（Reg3γ）在成骨细胞中大量表达；鉴于成骨细胞的功能发挥过程是在低氧状态下进行的，本课题发现，Reg3γ在成骨细胞中的表达主要受低氧诱导因子（HIF-1α）调控，且其可进入血液循环，可能在调节机体的基础及糖尿病状态下的糖代谢中发挥重要作用。因而，本课题将借助成骨细胞Reg3γ特异性敲除鼠，成骨细胞Vhl和Reg3γ双敲除鼠及其原代成骨细胞，深入研究：HIF-1α调控Reg3γ表达的分子机制及成骨细胞来源的Reg3γ参与调控基础及糖尿病状态下糖代谢的功能和分子机制。本项目如能实施，将揭示成骨细胞源性的Reg3γ参与调节糖代谢的功能和分子机制，可望为糖尿病等糖代谢性疾病提供新的治疗靶点。

The skeleton has emerged as an important regulator of systemic metabolism homeostasis. Although the critical role of osteocalcin in regulating energy metabolism has been established, recent reports also implicated osteocalcin-independent mechanisms in the glucose metabolism. In the preliminary study, we found that Reg3γ was abundantly expressed in osteoblasts. Furthermore, our studies also revealed that HIF-1α was a master transcriptional factor in regulating Reg3γ expression, osteoblast-derived Reg3γ could enter the blood and participated in systemic circulation, which might play an important function in regulating whole body glucose homeostasis physiologically, and under pathological conditions, such as diabetes. In the present study, we will use the osteoblast-specific Reg3γ-/- mice and the primary osteoblasts to uncover the molecular mechanisms by which HIF-1α regulats Reg3γ expression, as well as the function and underlying mechanisms by which osteoblast-derived Reg3γ in regulating glucose metabolism. So as to provide new ideas and theoretical bases for early intervention and treatment of metabolic disorders, such as diabetes.