title: The flavonoid glabridin attenuates 2-deoxy-D-ribose-induced oxidative             damage and cellular dysfunction in MC3T3-E1 osteoblastic cells.
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.
authors.affiliation: Department of Biomedical Science, College of Health Science,                     Korea University, Seongbuk-gu, Seoul 136‑703, Republic of Korea.
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Suh
authors.forename: Ara
authors.initials: A
authors.lastname: Ko
authors.forename: Donggeun
authors.initials: D
authors.lastname: Sul
authors.forename: Dalwoong
authors.initials: D
authors.lastname: Choi
authors.forename: Seung Kwan
authors.initials: SK
authors.lastname: Lee
authors.forename: Woon-Won
authors.initials: WW
authors.lastname: Jung
mesh_terms: D016475:3T3 Cells; D000111:Acetylcysteine / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003855:Deoxyribose / Q000009:adverse effects*; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation
chemical_list: D000111:Acetylcysteine; D000469:Alkaline Phosphatase; D000975:Antioxidants; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055419:Bone Morphogenetic Protein 7; D003094:Collagen; D003855:Deoxyribose; D005979:Glutathione Peroxidase; D007529:Isoflavones; D015675:Osteocalcin; D053495:Osteopontin; D053244:Osteoprotegerin; D010636:Phenols; D019869:Phosphatidylinositol 3-Kinases; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; C525820:bmp7 protein, mouse; C000606291:Sod1 protein, mouse; C494922:Akt2 protein, mouse; C107601:glabridin