Inhibitory effect of zinc on the advanced glycation end product-induced apoptosis of mouse osteoblastic cells

Abstract

Osteoporosis and diabetes have become serious health problems worldwide. Previous studies have suggested that diabetes is associated with osteoporosis and increased fracture risk. However, the mechanism underlying diabetes‑induced osteoporosis remains to be elucidated. Therefore, the present study aimed to examine the mechanism underlying diabetes‑induced osteoporosis, and determine the protective effects of zinc, which is known to be closely associated with osteoporosis and diabetes. The results of the present study demonstrated that zinc inhibited advanced glycation end product (AGE)‑induced MC3T3‑E1 cell apoptosis by attenuating the production of reactive oxygen species, inhibiting caspase‑3 and caspase‑9 activation, and inhibiting the release of cytochrome c from between the mitochondria and the cytosol. Furthermore, zinc was found to protect cells against AGE‑induced apoptosis via the mitogen‑activated protein kinase/extracellular signal‑regulated kinase and phosphoinositide 3‑kinase/AKT signaling pathways. In conclusion, these findings enable a better understanding of the mechanism underlying diabetes‑induced osteoporosis, and may indicate a novel target for its prevention and treatment.

Antioxidant Effect of Fructus Ligustri Lucidi Aqueous Extract in Ovariectomized Rats Is Mediated through Nox4-ROS-NF-κB Pathway

“…The increased production of ROS contributes to the release of Cyto-C from mitochondria into the cytosol (Liang et al, 2012), which facilitates cell apoptosis and osteoporosis (Xiong et al, 2015). Activation of NF-κB contributes to mitochondrial dysfunction, which further potentiates NF-κB activation (Cherry and Piantadosi, 2015).…”

Zinc against advanced glycation end products

“…Zinc administration significantly decreased this effect. Xiong et al assessed protective effects of zinc against AGE‑induced apoptosis and ROS generation. The authors reported that AGEs induce cell apoptosis and increase cellular ROS levels and suppress cell growth and viability, whereas, zinc administration prevents AGE‐induced cell apoptosis and the creation of ROS and improves cell viability.…”

“…Activation of survival signalling pathways, mitogen‐activated protein kinase/extracellular signal‐regulated kinase and phosphoinositide 3‐kinase/AKT signalling pathways, have been implicated to trigger anti‑apoptotic signal transduction pathways and to inhibit caspase‐3 formation/activity and delay of apoptosis, through ERK and Akt . Treatment with zinc substantially up regulates the expression levels of p‑ERK and p‑AKT in AGE‑treated cells and effectively protects the cells from AGE‑induced apoptosis …”

“…Multiple evidence has indicated the protective effects of zinc against several chronic diseases such as diabetes . Numerous in vitro and animal model studies have demonstrated the anti‐glycation impact of zinc …”

“…8,9 Numerous in vitro and animal model studies have demonstrated the anti-glycation impact of zinc. 10,11 Despite the large number of important researches, zinc has not been applied as a therapeutic intervention in humans in part due to the fact that information on its anti-glycation effects has not been yet summarized. Therefore, the present study was undertaken to organize the effects of zinc on the formation of AGEs.…”