Jingru Meng 1 , 5 , Xue Ma 1 , 5 , Ning Wang 1 , 5 , Min Jia 1 , Long Bi 2 , Yunying Wang 3 , Mingkai Li 1 , Huinan Zhang 1 , Xiaoyan Xue 1 , Zheng Hou 1 , Ying Zhou 1 , Zhibin Yu 3 , Gonghao He 4 , 6 , Xiaoxing Luo 1 , ∗
03 March 2016
Glucagon-like peptide 1 (GLP-1) plays an important role in regulating bone remodeling, and GLP-1 receptor agonist shows a positive relationship with osteoblast activity. However, GLP-1 receptor is not found in osteoblast, and the mechanism of GLP-1 receptor agonist on regulating bone remodeling is unclear. Here, we show that the GLP-1 receptor agonist exendin-4 (Ex-4) promoted bone formation and increased bone mass and quality in a rat unloading-induced bone loss model. These functions were accompanied by an increase in osteoblast number and serum bone formation markers, while the adipocyte number was decreased. Furthermore, GLP-1 receptor was detected in bone marrow stromal cells (BMSCs), but not in osteoblast. Activation of GLP-1 receptor by Ex-4 promoted the osteogenic differentiation and inhibited BMSC adipogenic differentiation through regulating PKA/β-catenin and PKA/PI3K/AKT/GSK3β signaling. These findings reveal that GLP-1 receptor regulates BMSC osteogenic differentiation and provide a molecular basis for therapeutic potential of GLP-1 against osteoporosis.
In this article, Luo and colleagues show that GLP-1 receptor agonist exendin-4 (Ex-4) increased bone mass in rat unloading-induced osteoporosis. Ex-4 promoted BMSC osteogenic differentiation and inhibited their adipogenic differentiation through regulating PKA/β-catenin and PKA/PI3K/AKT/GSK3β signaling. These findings reveal that GLP-1 receptor regulates BMSC osteogenic differentiation and provides a molecular basis for GLP-1 therapeutic potential against osteoporosis.