Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 cooperates with glycogen synthase kinase-3β to regulate osteogenesis of bone-marrow mesenchymal stem cells in type 2 diabetes ☆

Abstract Type 2 diabetes mellitus (T2DM) is associated with inhibited osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Brain and muscle ARNT-like protein 1 (BMAL1) has been linked to the T2DM-related bone remodeling, however, the specific mechanism is still unclear. Herein, we aimed to determine the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Inhibited osteogenesis and BMAL1 expression were showed in diabetic BMSCs. And while β-catenin and T cell factor (TCF) expression were decreased, the glycogen synthase kinase-3β (GSK-3β) and nemo-like kinase (NLK) expression were increased in diabetic BMSCs. Moreover, over-expression of BMAL1 led to recovered osteogenesis ability and activation of Wnt/β-catenin pathway, which was partially due to inhibition of GSK-3β caused by over-expression of BMAL1. Taken together, our findings provide new insights into the role of BMAL1 in T2DM-induced suppression of BMSCs osteogenesis. Over-expressed BMAL1 could recover BMSCs osteogenesis in T2DM partially by decreasing GSK-3β expression to activate Wnt/β-catenin pathway. BMAL1 may have a potential use in repairing diabetic bone metabolic disorders.