Background: Glucagon-like peptide-1(GLP-1) analogue, which act as endogenous intestinal hormone and promising antidiabetic drugs, have shown beneficial effects on bone metabolism in some clinical studies, but the molecular mechanism remains unclear. The aim of our study was to investigate whether GLP-1 could affect the “intestines-fat- bone axis” via Wnt/GSK-3β/β-catenin pathway.
Methods: Human ADSCs (hADSCs) were cultured and induced to osteogenic and adipogenic differentiation under high glucose condition. The cells was cultured with different dose of GLP-1, and treated with Wnt pathway agonist (LiCL) or inhibitor (DKK-1) respectively. In order to further explore the mechanisms, we use lentivirus to knockdown the core molecule (GSK-3β and DKK-1) of Wnt pathway. The Oil red O staining, Alizarin red staining, quantitative RT-PCR and Western blotting were also used.
Results: GLP-1 repressed induction of adipocyte differentiation biomarkers, and reduced endogenous lipoid deposits in cells. In addition, GLP-1 enhanced the expression of osteoblastogenic biomarkers such as OCN, Runx2 as well as Collagen I, which promoted osteoblastic mineralization. These impacts were substantially suppressed by the inhibitor of Wnt. The above results could be reversed when GSK-3β were silenced. It provide that GLP-1 promotes osteogenic differentiation of hADSCs via Wnt/GSK-3β/β-catenin pathway.
Y. Li: None. H. Fu: None. S. Luo: None. L. Wang: None. J. Chen: None. H. Lu: None.
Sun Yat-sen University (17YKZD23); National Natural Science Foundation of China (81670815); Natural Science Foundation of Guangdong Province (2016A030313279)