Fig. 2

Hyperglycemia affects bone formation, bone resorption, glucose metabolism, and lipid metabolism by disrupting the canonical Wnt pathway in osteoblasts, ST2 cells, BMSCs, MC3T3-E1 cells, and IDG-SW3 cells

Hyperglycemia-generated ROS and AGEs can inhibit the Wnt/β-catenin signaling pathway in a manner that inhibits expression of Wnt ligands and receptors, and increases expression of antagonists, thereby inhibiting bone formation and increasing bone resorption. In particular, decreases in Wnt10b and LRP5 affect glucose and lipid metabolism, as well as insulin secretion. Elevated glucose can directly act on IDG-SW3 cells to increase SOST expression, leading to increased RANKL expression, decreased glucose metabolism, and reduced insulin sensitivity. Simultaneously, increased levels of DKK-1 caused by high glucose will inhibit OPG secretion by osteoblasts and increase fasting plasma glucose levels (mainly in children and adolescents with T1DM)

Abbreviations: ST2cells, bone marrow stromal cells of ST2 mice; BMSCs, bone mesenchymal stem cells; MC3T3-E1 cells, mouse embryo osteoblast precursor cells; IDG-SW3 cells, osteocyte-like cell line; ROS, reactive oxygen species; AGEs, advanced glycation end products; RANKL, receptor activator of nuclear factor κB ligand; OPG, osteoprotegerin