High glucose microenvironments inhibit the proliferation and migration of bone mesenchymal stem cells by activating GSK3β

Diabetes mellitus involves metabolic changes that can impair bone repair. Bone mesenchymal stem cells (BMSCs) play an important role in bone regeneration. However, the bone regeneration ability of BMSCs is inhibited in high glucose microenvironments. It can be speculated that this effect is due to changes in BMSCs' proliferation and migration ability, because the recruitment of factors with an adequate number of MSCs and the microenvironment around the site of bone injury are required for effective bone repair. Recent genetic evidence has shown that the Cyclin D1 and the CXC receptor 4 (CXCR-4) play important roles in the proliferation and migration of BMSCs. In this study we determined the specific role of glycogen synthase kinase-3 beta (GSK3 beta) in the proliferation and migration of BMSCs in high glucose microenvironments. The proliferation and migration ability of BMSCs were suppressed under high glucose conditions. We showed that high glucose activates GSK3 beta but suppresses CXCR-4, beta-catenin, LEF-1, and cyclin D1. Inhibition of GSK3 beta by LiCl led to increased levels of beta-catenin, LEF-1, cyclin D1, and CXCR-4 expression. Our data indicate that GSK3 beta plays an important role in regulating the proliferation and migration of BMSCs by inhibiting cyclin D1 and CXCR-4 under high glucose conditions.