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.
Highlights
Osteoblast differentiation is a key process in bone formation and it is controlled by a complex signaling network with the interplay between many proteins and signaling molecules but mechanisms underlying these interactions are poorly understood [1]
In the present work we investigated the extent of DNA damage induced by oxidative stress during differentiation of MC3T3-E1 osteoblasts exposed to dexamethasone and 1,25-dihydroxywitamin D3, which are recognized RUNX2 modifiers
Differentiation of MC3T3-E1 Osteoblasts Is Associated with Production of Reactive Oxygen
Summary
Osteoblast differentiation is a key process in bone formation and it is controlled by a complex signaling network with the interplay between many proteins and signaling molecules but mechanisms underlying these interactions are poorly understood [1]. Oxidative stress in the cell can be operationally defined as a state, in which the production of reactive oxygen species (ROS) exceeds the efficacy of the cellular antioxidant system. This system comprises antioxidant enzymes, DNA damage response (DDR), including DNA repair and apoptosis, and small molecular weight antioxidants, including some vitamins, reduced glutathione and other molecules [3]. Autophagy was suggested to be major antioxidant mechanisms in neurodegenerative diseases [4]
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