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Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):355-361. doi: 10.1016/j.bbrc.2018.11.040. Epub 2018 Nov 13.

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

Abstract

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.

KEYWORDS:

Caspase-3; Dexamethasone; Klotho; NF-κB; Osteoblast

PMID:
30442365
DOI:
10.1016/j.bbrc.2018.11.040
[Indexed for MEDLINE]

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