Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization

Abstract Although deoxyribonucleic acid (DNA) is the genetic coding for the very essence of life, these macromolecules or components thereof are not necessarily lost after a cell dies. There appears to be a link between extracellular DNA and biomineralization. Here the authors demonstrate that extra...

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Main Authors: Min‐juan Shen, Kai Jiao, Chen‐yu Wang, Hermann Ehrlich, Mei‐chen Wan, Dong‐xiao Hao, Jing Li, Qian‐qian Wan, Lige Tonggu, Jian‐fei Yan, Kai‐yan Wang, Yu‐xuan Ma, Ji‐hua Chen, Franklin R. Tay, Li‐na Niu
Format: Article
Language:English
Published: Wiley 2022-02-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202103693
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author Min‐juan Shen
Kai Jiao
Chen‐yu Wang
Hermann Ehrlich
Mei‐chen Wan
Dong‐xiao Hao
Jing Li
Qian‐qian Wan
Lige Tonggu
Jian‐fei Yan
Kai‐yan Wang
Yu‐xuan Ma
Ji‐hua Chen
Franklin R. Tay
Li‐na Niu
author_facet Min‐juan Shen
Kai Jiao
Chen‐yu Wang
Hermann Ehrlich
Mei‐chen Wan
Dong‐xiao Hao
Jing Li
Qian‐qian Wan
Lige Tonggu
Jian‐fei Yan
Kai‐yan Wang
Yu‐xuan Ma
Ji‐hua Chen
Franklin R. Tay
Li‐na Niu
author_sort Min‐juan Shen
collection DOAJ
description Abstract Although deoxyribonucleic acid (DNA) is the genetic coding for the very essence of life, these macromolecules or components thereof are not necessarily lost after a cell dies. There appears to be a link between extracellular DNA and biomineralization. Here the authors demonstrate that extracellular DNA functions as an initiator of collagen intrafibrillar mineralization. This is confirmed with in vitro and in vivo biological mineralization models. Because of their polyanionic property, extracellular DNA molecules are capable of stabilizing supersaturated calcium phosphate solution and mineralizing 2D and 3D collagen matrices completely as early as 24 h. The effectiveness of extracellular DNA in biomineralization of collagen is attributed to the relatively stable formation of amorphous liquid droplets triggered by attraction of DNA to the collagen fibrils via hydrogen bonding. These findings suggest that extracellular DNA is biomimetically significant for fabricating inorganic–organic hybrid materials for tissue engineering. DNA‐induced collagen intrafibrillar mineralization provides a clue to the pathogenesis of ectopic mineralization in different body tissues. The use of DNase for targeting extracellular DNA at destined tissue sites provides a potential solution for treatment of diseases associated with ectopic mineralization.
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spelling doaj.art-c0af4d0dbd5b4cbd9e24499abcdca9b02022-12-21T17:24:52ZengWileyAdvanced Science2198-38442022-02-0195n/an/a10.1002/advs.202103693Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic MineralizationMin‐juan Shen0Kai Jiao1Chen‐yu Wang2Hermann Ehrlich3Mei‐chen Wan4Dong‐xiao Hao5Jing Li6Qian‐qian Wan7Lige Tonggu8Jian‐fei Yan9Kai‐yan Wang10Yu‐xuan Ma11Ji‐hua Chen12Franklin R. Tay13Li‐na Niu14National Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaInstitute of Electronic and Sensor Materials TU Bergakademie Freiberg Freiberg 09599 GermanyNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaSchool of Medicine University of Washington Seattle WA 98195 USANational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaNational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaThe Dental College of Georgia Augusta University Augusta GA 30912 USANational Clinical Research Center for Oral Diseases & State Key Laboratory of Military Stomatology & Shaanxi Key Laboratory of Stomatology, School of Stomatology The Fourth Military Medical University Xi'an Shaanxi 710032 P. R. ChinaAbstract Although deoxyribonucleic acid (DNA) is the genetic coding for the very essence of life, these macromolecules or components thereof are not necessarily lost after a cell dies. There appears to be a link between extracellular DNA and biomineralization. Here the authors demonstrate that extracellular DNA functions as an initiator of collagen intrafibrillar mineralization. This is confirmed with in vitro and in vivo biological mineralization models. Because of their polyanionic property, extracellular DNA molecules are capable of stabilizing supersaturated calcium phosphate solution and mineralizing 2D and 3D collagen matrices completely as early as 24 h. The effectiveness of extracellular DNA in biomineralization of collagen is attributed to the relatively stable formation of amorphous liquid droplets triggered by attraction of DNA to the collagen fibrils via hydrogen bonding. These findings suggest that extracellular DNA is biomimetically significant for fabricating inorganic–organic hybrid materials for tissue engineering. DNA‐induced collagen intrafibrillar mineralization provides a clue to the pathogenesis of ectopic mineralization in different body tissues. The use of DNase for targeting extracellular DNA at destined tissue sites provides a potential solution for treatment of diseases associated with ectopic mineralization.https://doi.org/10.1002/advs.202103693amorphous calcium phosphatebiomineralizationcollagenectopic calcificationextracellular nucleic acids
spellingShingle Min‐juan Shen
Kai Jiao
Chen‐yu Wang
Hermann Ehrlich
Mei‐chen Wan
Dong‐xiao Hao
Jing Li
Qian‐qian Wan
Lige Tonggu
Jian‐fei Yan
Kai‐yan Wang
Yu‐xuan Ma
Ji‐hua Chen
Franklin R. Tay
Li‐na Niu
Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization
Advanced Science
amorphous calcium phosphate
biomineralization
collagen
ectopic calcification
extracellular nucleic acids
title Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization
title_full Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization
title_fullStr Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization
title_full_unstemmed Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization
title_short Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization
title_sort extracellular dna a missing link in the pathogenesis of ectopic mineralization
topic amorphous calcium phosphate
biomineralization
collagen
ectopic calcification
extracellular nucleic acids
url https://doi.org/10.1002/advs.202103693
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