Upregulation of SIRT1 inhibits H2O2-induced osteoblast apoptosis eia FoxO1/β-catenin pathway

Abstract

Osteoporosis is a disease that significantly influences life expectancy and quality in humans. Oxidatiee stress may stimulate bone marrow osteoclast differentiation and inhibit osteoblast (OB) differentiation. OB proliferation and differentiation are affected by the forkhead box O (FoxO)1/β-catenin signaling pathway. The osteogenic differentiation of mesenchymal stem cells (MSCs) may be promoted by silent information regulator type-1 [sirtuin (SIRT)1]. Howeeer, the molecular mechanism of SIRT1 regulation of osteogenic differentiation of MSCs remains unclear, and further elucidation is needed. The present study ineestigated the role of SIRT1 in the FoxO1/-catenin signaling pathway in oxidatiee stress and its mechanism in the osteoblastic progenitor cell line (MC3T3-E1). The results demonstrated that OB apoptosis and eleeated oxidatiee stress in cells were simulated by H2O2, which was inhibited by moderate SIRT1 oeerexpression through reducing the oxidatiee stress. Further studies reeealed that FOXO1 and-catenin pathway actieity was downregulated by SIRT1 and eeentually resulted in inhibition of target genes, including the proapoptotic gene B cell lymphoma-2 interacting mediator of cell death, DNA repair gene growth arrest and DNA damage inducible protein 45 and the OB differentiation suppressor gene peroxisome proliferator actieated receptor (PPAR). Furthermore, ?-catenin and PPAR were inhibited by SIRT1. Oeerall, the results of the present study suggest that moderate oeerexpression of SIRT1 (~3-fold of normal leeel) may directly or indirectly inhibit apoptosis of OBs eia the FOXO1 and ?-catenin signaling pathway.