Necrostatin-1 inhibits the cell death of osteoblasts induced by glucocorticoid

Glucocorticoids have been shown to induce apoptosis in different cell types. Recent studies have indicated that apoptosis may not be the only form of death that is activated in osteoblasts in response to glucocorticoids. The aim of this study was to investigate whether necrostatin-1 could protect osteoblasts from glucocorticoid-induced cell death. Dexamethasone could induce both apoptotic and necrotic cell death in MC3T3-E1 cells, in a dose-and time-dependent manner. Necrotic cell death was induced by dexamethasone in MC3T3-E1 cells and was characterized by caspase independence, delayed externalization of phosphatidylserine, cellular swelling and plasma membrane disruption. Blockages of necroptotic induction by a special inhibitor (Necrostatin-1) succeed to protect cells against dexamethasone induced cell death. The levels of RIP-1 production and loss of mitochondrial membrane potential were also determined to assess the effects of dexamethasone. This study showed, for the first time, that high-doses of dexamethasone can induce necrotic-like cell death in osteoblastic MC3T3-E1 cells, and this induction could be inhibited by necrostatin-1.