Diabetic osteoporosis (DOP) is attributed to the aberrant physiological function of bone marrow mesenchymal stem cells (BMSCs) under high glucose (HG) environment. MicroRNAs (miRNAs) are involved in the pathological processes of DOP. We aimed to explore the underlying mechanism of miRNA in DOP. BMSCs were cultured in osteogenic medium with HG to induce osteogenic differentiation, and the interaction between miR-493-5p and ZEB2 was assessed by luciferase assay. Herein, we found miR-493-5p is gradually reduced during osteogenic differentiation in BMSCs. HG treatment inhibits osteogenic differentiation and induces an up-regulation of miR-493-5p leading to reduced level of its downstream target ZEB2. Inhibition of miR-493-5p attenuates HG-induced osteogenic differentiation defects by upregulation of ZEB2. Mechanistically, miR-493-5p/ZEB2 signalling mediates HG-inhibited osteogenic differentiation by inactivation of Wnt/β-catenin signalling. More importantly, knockdown of miR-493-5p therapeutically alleviated the DOP condition in mice. HG prevents BMSCs osteogenic differentiation via up-regulation of miR-493-5p, which results in reduced level of ZEB2 by directly targeting its 3′-untranslated region of mRNA. Thus, miR-493-5p/ZEB2 is a potential therapeutic target and provides novel strategy for the treatment and management of DOP.

The present study aimed to investigate the effects of vitamin B12 on islet β-cell (INS-1) induced by streptozotocin (STZ) and the potential mechanisms. In this study, CCK8 was used to detect cell viability and TUNEL assay was used to detect apoptosis levels of treated INS-1 cells. The expression level of oxidative stress factors was measured by ELISA. Furthermore, western blot assay was used to detect the expression of PPAR-γ and apoptotic factors in treated INS-1 cells. Vitamin B12 improves STZ-induced insulin secretion in INS-1 cells, oxidative stress injury and apoptosis. Moreover, Vitamin B12 can activate the PPAR-γ signaling pathway and inhibit STZ-induced INS-1 cell damage. Taken together, our study demonstrated that vitamin B12 inhibits streptozotocin-induced islet β-cell oxidative stress and apoptosis by activating PPAR-γ signaling pathway.