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Published on: September 1, 2019
RUNX2: A Master Bone Growth Regulator That May Be Involved in the DNA Damage Response
Daniel Wysokinski1, Elzbieta Pawlowska, Janusz Blasiak
11 Department of Molecular Genetics, University of Lodz , Lodz, Poland .
Abstract:
RUNX2 is a member of the RUNX family of transcription factors, also containing the RUNX1 and RUNX3 proteins. These factors control the expression of genes essential for proper development in many cell lineages. RUNX2 plays a crucial role in the proliferation and differentiation of osteoblasts, required for bone formation. The cellular level of RUNX2 oscillates in a cell phase-specific manner, reaching a maximum at G2/M in some cells and overexpression of RUNX2 in osteoblasts blocked G1 to S phase progression. Recent studies have shown that RUNX2 may interact with p53 and change the activity of a histone deacetylase. Moreover, RUNX2 may act as an oncogene in cancer transformation, inevitably associated with genomic instability evoked by increased occurrence of DNA damage. We showed that some RUNX2 modifiers changed the sensitivity of differentiating preosteoblasts to DNA damage induced by oxidative stress. All these data suggest the involvement of RUNX2 in cellular DNA damage response (DDR), which is particularly important in osteogenesis as the process of osteoblast differentiation is associated with increasing oxidative stress. However, the mechanism underlying DDR involvement of RUNX2 is unknown. The basic question, whether RUNX2 plays a positive or destructive role in DDR in differentiating cells is still open.
Insights
RUNX2, a key factor in bone formation, is investigated for its role in DNA damage response (DDR). This research explores how RUNX2 influences osteoblast differentiation and cellular sensitivity to DNA damage, particularly oxidative stress.
Area of Science:
- Molecular Biology
- Cell Biology
- Developmental Biology
Background:
- RUNX2 is a critical transcription factor for osteoblast proliferation and differentiation in bone formation.
- RUNX2 levels fluctuate during the cell cycle and can impact cell cycle progression.
- Emerging evidence suggests RUNX2's involvement in cancer and genomic instability.
Purpose of the Study:
- To investigate the role of RUNX2 in the cellular DNA damage response (DDR).
- To understand RUNX2's function in differentiating cells, especially during osteogenesis under oxidative stress.
- To elucidate the mechanism of RUNX2's involvement in DDR.
Main Methods:
- Analysis of RUNX2 expression patterns during the cell cycle.
- Investigating RUNX2 interactions with proteins like p53 and histone deacetylases.
- Assessing the impact of RUNX2 modifiers on preosteoblast sensitivity to oxidative stress-induced DNA damage.
Main Results:
- RUNX2's cellular levels exhibit cell phase-specific oscillations.
- RUNX2 overexpression can impede G1 to S phase progression in osteoblasts.
- RUNX2 modifiers alter the sensitivity of differentiating preosteoblasts to oxidative DNA damage.
Conclusions:
- RUNX2 is implicated in the cellular DNA damage response (DDR).
- RUNX2's role in DDR is crucial for osteogenesis, which involves oxidative stress.
- The precise function of RUNX2 in DDR within differentiating cells remains an open question.
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