Klotho prevents DEX-induced apoptosis in MC3T3-E1 osteoblasts through the NF-κB signaling pathway

Dexamethasone (DEX) is a commonly used anti-inflammatory drug and an immunosuppressive drug used in clinical practice to treat a variety of diseases. Glucocorticoid-induced osteoporosis (GIOP) is a consequence of high dose, or a long-term low dose use of glucocorticoids (GCs). These treatment regimens can cause a variety of bone-related adverse effects, leading to increased osteoblast and bone cell apoptosis. Evidence suggests that klotho (KL) can inhibit GIOP. It is unknown whether KL attenuates DEX-induced apoptosis in MC3T3-E1 cells or the underlying mechanisms involved. In the present study, we found that MC3T3-E1 cells pretreated with DEX led to the up-regulation of cleaved-caspase-3, and down-regulation of caspase-3, which were inhibited by KL transfection. Furthermore, flow cytometry and western blot analysis revealed that the NFκB inhibitor pyrrolidine dithiocarbamate (PDTC) could restore the DEX-induced caspase-3 decrease and inhibit the DEX-induced cleaved caspase-3 increase. We observed that DEX stimulated the degradation of IκBα(NFκB inhibitor α) and the translocation of NFκB, which were suppressed by KL transfection. These findings therefore, indicate a protective role for KL against osteoblastic cell apoptosis induced by DEX, via the NF-κB signaling pathway. •Klotho can inhibit DEX-induced apoptosis of MC3T3-E1 osteoblasts by inhibiting the expression of caspase-3.•NF-κB inhibitor PDTC reduced the number of DEX-induced apoptotic cells and attenuated the activity of caspase-3.•Klotho can inhibit IκB degradation, NF-κB nuclear translocation, and p65 phosphorylation in DEX-induced MC3T3-E1 apoptosis.