High glucose promotes apoptosis and autophagy of MC3T3-E1 osteoblasts.

Abstract

Diabetes and osteoporosis are common metabolic diseases. Abnormal high glucose can lead to the apoptosis of osteoblasts. Autophagy is a highly conserved cellular process that degrades proteins or organelles. In the present study, we comparatively analyzed the effects of high glucose and glucose fluctuation on apoptosis and autophagy of MC3T3-E1 osteoblasts. MC3T3-E1 cells were respectively treated with different concentrations of D-glucose: 5.5 mM for the control group, 25 mM for the high glucose group and 5.5/25 mM for the glucose fluctuation group. High glucose and glucose fluctuation decreased MC3T3-E1 proliferation and activated autophagy. Also, high glucose and glucose fluctuation might induce the production of reactive oxygen species, decline the mitochondrial membrane potential and trigger apoptosis. The differences in the glucose fluctuation treatment group were more significant. Moreover, N-acetylcysteine, an antioxidant reagent, dramatically eliminated the intracellular reactive oxygen species induced by high glucose and glucose fluctuation, and significantly inhibited the autophagy and apoptosis in MC3T3-E1 osteoblasts. Furthermore, treatment with chloroquine, an inhibitor of autophagy, significantly increased the apoptosis of MC3T3-E1 osteoblasts. High glucose, especially high glucose fluctuation, inhibits proliferation and promotes apoptosis and autophagy of MC3T3-E1 osteoblasts. This may occur through inducing oxidative stress and mitochondrial damage in the osteoblasts.