Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin.
Activation of GLP-1 Receptor Promotes Bone Marrow Stromal Cell Osteogenic Differentiation through β-Catenin.
复制标题
GLP-1受体的激活通过β-Catenin促进骨髓基质细胞成骨分化
DOI：
10.1016/j.stemcr.2016.02.002
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发表时间：
2016-04-12
影响因子：
5.9
通讯作者：
Luo X
中科院分区：
文献类型：
--
作者：
Meng J;Ma X;Wang N;Jia M;Bi L;Wang Y;Li M;Zhang H;Xue X;Hou Z;Zhou Y;Yu Z;He G;Luo X
胰高血糖素样肽1 （Glucagon-like peptide 1, GLP-1）在骨重塑调节中起重要作用，GLP-1受体激动剂与成骨细胞活性呈正相关。然而，在成骨细胞中未发现GLP-1受体，GLP-1受体激动剂调节骨重塑的机制尚不清楚。在此，我们发现GLP-1受体激动剂exendin-4 （Ex-4）促进骨形成，增加骨质量和骨量。这些功能伴随着成骨细胞数量和血清骨形成标志物的增加，而脂肪细胞数量减少。此外，GLP-1受体在骨髓基质细胞（BMSCs）中检测到，而在成骨细胞中未检测到。Ex-4激活GLP-1受体通过调控PKA/β-catenin和PKA/PI3K/AKT/GSK3β信号通路促进成骨分化，抑制BMSC成脂分化。这些发现揭示了GLP-1受体调控BMSC成骨分化，为GLP-1治疗骨质疏松提供了分子基础。GLP-1受体激动剂exendin-4改善骨质疏松GLP-1受体激活增强BMSC成骨分化GLP-1受体激活抑制BMSC成脂分化exendin-4通过β-catenin促进骨形成，增加骨量在本文中，Luo和同事发现GLP-1受体激动剂exendin-4 （Ex-4）增加大鼠骨质疏松症的骨量。Ex-4通过调节PKA/β-catenin和PKA/PI3K/AKT/GSK3β信号通路促进BMSC成骨分化，抑制其成脂分化。这些发现揭示了GLP-1受体调控BMSC成骨分化，为GLP-1治疗骨质疏松提供了分子基础。
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. GLP-1 receptor agonist exendin-4 improved unloading-induced bone loss Activation of GLP-1 receptor enhanced BMSC osteogenic differentiation Activation of GLP-1 receptor inhibited BMSC adipogenic differentiation Exendin-4 promoted bone formation and increased bone mass through β-catenin 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.