N-Acetylcysteine Attenuates the Prednisolone-Induced Osteoporosis via Rescuing the Nuclear Factor Erythroid 2-Related Factor 2-Antioxidant Responsive Element Axis Activity in Mice

Abstract

We aimed to investigate the effect and potentialmechanism of N-acetylcysteine (NAC), as an antioxidant, on prednisolone-induced osteoporosis. C57bl/6 mice were subcutaneously delivered with prednisolone to induce osteoporosis. The bone marrow mesenchymal stem cells (MSCs) from mice were induced to osteoblast differentiation and treated with prednisolone in vitro. Meanwhile, the NAC or Nrf2 activator Oltipraz (OPZ) was supplied in the prednisolone treatment. The osteoporosis was determined by bone mineral density, trabecular bone volume, and the parameters of bone absorption and formation. Additionally, the Nrf2, ARE-driven genes HMOX-1, GCLC, ME1, and NQO1 expression were measured by western blot or qRT-PCR. The reactive oxygen species (ROS) was measured by a commercial kit. Prednisolone significantly deceased the bone volume, osteoblastic bone formation, osteogenesis of MSCs, and the expression of Nrf2 and ARE-driven genes. On the contrary, prednisolone promoted ROS production and osteoclastic bone absorption. However, the supplement of NAC or OPZ with prednisolone treatment could markedly rescue the Nrf2 and ARE-droven genes expression, reduce the ROS, alleviate the bone loss, and protect the osteogenesis of MSCs. Our results demonstrated that NAC presented a protective property of Nrf2-ARE axis and resulting prevention of prednisolone-induced osteoporosis.