Hyperglycemia induces endoplasmic reticulum stress-dependent CHOP expression in osteoblasts

Diabetic osteoporosis is a metabolic bone disease responsible for global health problems. Hyperglycemia induces osteopenia, increases bone fragility and unbalances the coupling of osteoblasts and osteoclasts. The mechanism is, however, unknown. For the purpose of this study, we hypothesized that hyperglycemia destroys endoplasmic reticulum (ER) homeostasis, activates C/EBP-homologous protein (CHOP) and induces osteoblast apoptosis under diabetic conditions. Diabetic rats were created by injecting streptozotocin (STZ) 65 mg/kg intraperitoneally and their osteoblasts were cultured under high-glucose medium in vitro. The bone mineral density (BMD) and pathological changes of the rats' femurs were observed. The expression of CHOP in osteoblasts was assayed using immunohistochemistry and western blot analysis. Six weeks after diabetic model establishment, a significant decrease was found in the BMD of the diabetic rat femurs, and the numbers of osteoblasts under cortical bone were also reduced. The expression of the ER stress regulator CHOP in osteoblasts of diabetic rats or high-glucose medium was also elevated (P<0.01). The present results demonstrated that hyperglycemia elevated the expression of CHOP and finally led to osteoporosis. This suggested that elevating the expression of CHOP may play a role in diabetic osteoporosis.