title: Sciadopitysin protects osteoblast function via its antioxidant activity in MC3T3-E1 cells.
abstract: Age-related osteoblast dysfunction is the main cause of age-related bone loss in both men and women. In the present study, the effect of sciadopitysin, a type of biflavonoids, on osteoblast function was investigated in osteoblastic MC3T3-E1 cells. Sciadopitysin caused a significant elevation of alkaline phosphatase activity, collagen synthesis, osteocalcin production, mineralization, and glutathione content in the cells (P<0.05). Sciadopitysin also decreased the production of tumor necrosis factor-a (TNF-α) induced by antimycin A, a mitochondrial electron transport inhibitor. We investigated the protective effects of sciadopitysin on antimycin A-induced toxicity in osteoblastic MC3T3-E1 cells. Exposure of MC3T3-E1 cells to antimycin A caused a significant reduction in osteoblast dysfunction. However, pretreatment with sciadopitysin prior to antimycin A exposure significantly reduced antimycin A-induced cell damage by preventing mitochondrial membrane potential dissipation, adenosine triphosphate (ATP) loss, reactive oxygen species (ROS) release, and nitrotyrosine increase, suggesting that sciadopitysin may be useful for protecting mitochondria against a burst of oxidative stress. Moreover, sciadopitysin increased phosphorylation of cAMP-response element-binding protein (CREB) inhibited by antimycin A. Our results demonstrate that sciadopitysin may reduce or prevent osteoblasts degeneration.
authors.affiliation: Research Institute of Endocrinology, Kyung Hee University Hospital, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-702, Republic of Korea.
authors.forename: Kwang Sik
authors.initials: KS
authors.lastname: Suh
authors.forename: Young Soon
authors.initials: YS
authors.lastname: Lee
authors.forename: Young Seol
authors.initials: YS
authors.lastname: Kim
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Choi
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D044946:Biflavonoids / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010766:Phosphorylation
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D017362:Cyclic AMP Response Element-Binding Protein; C086243:sciadopitysin; D000968:Antimycin A
keywords: ALP; ATP; CREB; Differentiation; GSH; MC3T3-E1 cells; MMP; MPT; Mitochondrial dysfunction; Oxidative stress; PGC-1α; ROS; Sciadopitysin; TNF-α; adenosine triphosphate; alkaline phosphatase; cAMP-response element-binding protein; mitochondrial membrane potential; mitochondrial permeability transition; peroxisome proliferator-activated receptor gamma coactivator; reactive oxygen species; reduced glutathione; tumor necrosis factor-α