title: Dexamethasone and 1,25-dihydroxyvitamin D3 reduce oxidative stress-related DNA damage in differentiating osteoblasts.
abstract: The process of osteoblast differentiation is regulated by several factors, including RUNX2. Recent reports suggest an involvement of RUNX2 in DNA damage response (DDR), which is important due to association of differentiation with oxidative stress. In the present work we explore the influence of two RUNX2 modifiers, dexamethasone (DEX) and 1,25-dihydroxyvitamin D3 (1,25-D3), in DDR in differentiating MC3T3-E1 preosteoblasts challenged by oxidative stress. The process of differentiation was associated with reactive oxygen species (ROS) production and tert-butyl hydroperoxide (TBH) reduced the rate of differentiation. The activity of alkaline phosphatase (ALP), a marker of the process of osteoblasts differentiation, increased in a time-dependent manner and TBH further increased this activity. This may indicate that additional oxidative stress, induced by TBH, may accelerate the differentiation process. The cells displayed changes in the sensitivity to TBH in the course of differentiation. DEX increased ALP activity, but 1,25-D3 had no effect on it. These results suggest that DEX might stimulate the process of preosteoblasts differentiation. Finally, we observed a protective effect of DEX and 1,25-D3 against DNA damage induced by TBH, except the day 24 of differentiation, when DEX increased the extent of TBH-induced DNA damage. We conclude that oxidative stress is associated with osteoblasts differentiation and induce DDR, which may be modulated by RUNX2-modifiers, DEX and 1,25-D3.
authors.affiliation: Department of Orthodontics, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland. elzbieta.pawlowska@umed.lodz.pl.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Pawlowska
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. dwysokinski@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wysokiński
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. ptokarz@biol.biol.uni.lodz.pl.
authors.forename: Paulina
authors.initials: P
authors.lastname: Tokarz
authors.affiliation: Department of Comparative Endocrinology, Medical University of Lodz, Zeligowskiego 7/9, 90-752 Lodz, Poland. agnieszka.piastowska@umed.lodz.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Piastowska-Ciesielska
authors.affiliation: Department of Pediatric Dentistry, Medical University of Lodz, Pomorska 251, 92-216 Lodz, Poland. joanna.szczepanska@umed.lodz.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczepanska
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. janusz.blasiak@biol.uni.lodz.pl.
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D017382:Reactive Oxygen Species; C493716:Runx2 protein, mouse; D003907:Dexamethasone; D020122:tert-Butylhydroperoxide; D000469:Alkaline Phosphatase; D002117:Calcitriol