International Journal of Molecular Medicine 2013-01-01

The flavonoid glabridin attenuates 2-deoxy-D-ribose-induced oxidative damage and cellular dysfunction in MC3T3-E1 osteoblastic cells.

Hyun-Sook Kim, Kwang Sik Suh, Ara Ko, Donggeun Sul, Dalwoong Choi, Seung Kwan Lee, Woon-Won Jung

Index: Int. J. Mol. Med. 31(1) , 243-51, (2013)

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Abstract

Reducing sugar 2-deoxy-D-ribose (dRib) produces reactive oxygen species (ROS) through autoxidation and protein glycosylation and causes dysfunction of osteoblasts. In the present study, glabridin, a natural flavonoid, was investigated to determine whether it could influence dRib-induced oxidative damage and cellular dysfunction in the MC3T3-E1 mouse osteoblastic cell line. Osteoblastic cells were treated with dRib in the presence or absence of glabridin. Cell viability, apoptosis, ROS production and mitochondrial membrane potential (ΔΨm) were subsequently examined. It was observed that dRib reduced cell survival and ΔΨm, while it markedly increased intracellular levels of ROS and apoptosis. However, pretreatment of cells with glabridin attenuated all the dRib-induced effects. The antioxidant N-acetyl-L-cysteine (NAC) also prevented dRib-induced oxidative cell damage. In addition, treatment with glabridin resulted in a significant elevation of alkaline phosphatase (ALP) activity, collagen contents and osteoblast differentiation genes [ALP, collagen, osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC)] and bone morphogenetic protein (BMP) genes (BMP2, BMP4 and BMP7). In mechanistic studies of the antioxidative potential of glabridin, we found that glabridin activated dRib-induced decreased expression of phosphatidylinositol 3'-kinase (PI3K) and protein kinase B 2 (AKT2) genes, which are master regulators of survival-related signaling pathways. Glabridin also upregulated the gene expression of antioxidant enzymes, superoxide dismutase 1 (SOD1) and glutathione peroxidase 4 (GPX4), which were inhibited by dRib. Taken together, these results suggest that glabridin attenuates dRib-induced cell damage in osteoblastic cells and may be useful for the treatment of diabetes-related bone disease.