Irradiation inhibits the maturation and mineralization of osteoblasts via the activation of Nrf2/HO-1 pathway

作者: Sung-Ho Kook , Kyoung-A Kim , Hyeok Ji , Daewoo Lee , Jeong-Chae Lee

DOI: 10.1007/S11010-015-2559-Z

关键词:

摘要: Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) regulates the induction of antioxidant gene expression and protects cells against oxidative injury. However, there are controversial findings regarding roles Nrf2 on bone metabolism under stress. The role differentiation radiation-exposed osteoblasts is also unclear. We investigated whether negatively or positively affects osteoblast in response to irradiation. Irradiation inhibited MC3T3-E1 a dose-dependent manner. This inhibition was evidenced by irradiation-mediated decreases bone-like nodule formation, alkaline phosphatase (ALP) activity, calcium accumulation, markers, such as ALP, osteocalcin, osteopontin, sialoprotein, osterix, Runx2. These reductions were accompanied increased heme oxygenase-1 (HO-1), accumulation cellular oxidants, depletion defense enzymes. siRNA-mediated silencing markedly reversed negative effect irradiation cells, leading decrease HO-1 an increase Runx2 levels. Irradiation-mediated levels osteocalcin mRNA, but not protein, significantly inhibitor, zinc protoporphyrin IX. Furthermore, N-acetyl cysteine restored all changes induced near-normal cells. results demonstrate that inhibits mineralization through stress-mediated activation Nrf2/HO-1 pathway.

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