Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization.
Adolescent
Adult
Aged
Animals
Biomineralization
Blood Vessels
/ metabolism
Cattle
Cell Line
Cells, Cultured
Collagen
/ metabolism
DNA Damage
Extracellular Matrix
/ metabolism
Female
Humans
Male
Mice
Middle Aged
Osteoblasts
/ metabolism
Oxidative Stress
Poly Adenosine Diphosphate Ribose
/ metabolism
Rats
Rats, Wistar
Sheep
Vascular Calcification
/ metabolism
DNA damage
bone
poly(ADP-ribose)
vascular smooth muscle cell
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
11 06 2019
11 06 2019
Historique:
received:
23
05
2018
revised:
03
04
2019
accepted:
09
05
2019
entrez:
13
6
2019
pubmed:
13
6
2019
medline:
4
8
2020
Statut:
ppublish
Résumé
Biomineralization of the extracellular matrix is an essential, regulated process. Inappropriate mineralization of bone and the vasculature has devastating effects on patient health, yet an integrated understanding of the chemical and cell biological processes that lead to mineral nucleation remains elusive. Here, we report that biomineralization of bone and the vasculature is associated with extracellular poly(ADP-ribose) synthesized by poly(ADP-ribose) polymerases in response to oxidative and/or DNA damage. We use ultrastructural methods to show poly(ADP-ribose) can form both calcified spherical particles, reminiscent of those found in vascular calcification, and biomimetically calcified collagen fibrils similar to bone. Importantly, inhibition of poly(ADP-ribose) biosynthesis in vitro and in vivo inhibits biomineralization, suggesting a therapeutic route for the treatment of vascular calcifications. We conclude that poly(ADP-ribose) plays a central chemical role in both pathological and physiological extracellular matrix calcification.
Identifiants
pubmed: 31189100
pii: S2211-1247(19)30658-8
doi: 10.1016/j.celrep.2019.05.038
pmc: PMC6581741
pii:
doi:
Substances chimiques
Poly Adenosine Diphosphate Ribose
26656-46-2
Collagen
9007-34-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3124-3138.e13Subventions
Organisme : British Heart Foundation
ID : RG/17/2/32808
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J007692/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/15/38/31466
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/10/43/28390
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/15/47/31646
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M01066X/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.