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Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization.
Karin H Müller1, Robert Hayward2, Rakesh Rajan1
1Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Cell Reports
|June 13, 2019
Summary
Extracellular poly(ADP-ribose) synthesis is linked to bone and vascular calcification. Inhibiting this process offers a potential therapeutic strategy for treating vascular calcifications.
Area of Science:
- Biochemistry
- Cell Biology
- Biomineralization
Background:
- Extracellular matrix biomineralization is crucial but poorly understood.
- Dysregulated mineralization in bone and vasculature causes severe health issues.
Purpose of the Study:
- To elucidate the chemical and cell biological mechanisms of mineral nucleation in extracellular matrix.
- To investigate the role of poly(ADP-ribose) in biomineralization.
Main Methods:
- Utilized ultrastructural methods to analyze calcification processes.
- Investigated poly(ADP-ribose) synthesis in response to cellular damage.
- Employed in vitro and in vivo models to assess the impact of inhibiting poly(ADP-ribose) biosynthesis.
Main Results:
- Extracellular poly(ADP-ribose) is associated with both vascular and bone biomineralization.
- Poly(ADP-ribose) can form calcified spherical particles and biomimetically calcify collagen fibrils.
- Inhibition of poly(ADP-ribose) biosynthesis effectively reduces biomineralization in vitro and in vivo.
Conclusions:
- Poly(ADP-ribose) plays a central chemical role in physiological and pathological extracellular matrix calcification.
- Targeting poly(ADP-ribose) synthesis presents a potential therapeutic avenue for vascular calcification.
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