@article{df8222f215704981a4d66f6f40f05302,
title = "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 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.",
keywords = "amorphous calcium phosphate, biomineralization, collagen, ectopic calcification, extracellular nucleic acids",
author = "Shen, {Min juan} and Kai Jiao and Wang, {Chen yu} and Hermann Ehrlich and Wan, {Mei chen} and Hao, {Dong xiao} and Jing Li and Wan, {Qian qian} and Lige Tonggu and Yan, {Jian fei} and Wang, {Kai yan} and Ma, {Yu xuan} and Chen, {Ji hua} and Tay, {Franklin R.} and Niu, {Li na}",
note = "Funding Information: M.‐j.S., K.J., and C.‐y.W. contributed equally to this work. The authors thank S.Z. for assistance in the molecular dynamic simulations. This work was supported by grants 81722015, 81870805, 81870787, and 81720108011 from National Natural Science Foundation of China, grant 2020TD‐033 from the Shaanxi Key Scientific and Technological Innovation Team, the Youth Innovation Team of Shaanxi Universities and by grant 2021JC‐34 from Distinguished Young Scientists Foundation of Shaanxi Province. H.E. was funded by a Polish Honorable Alexander von Humboldt Fellowship (FNP, Poland) as well as MAESTRO Project (NCN, Poland). All animal experiments were approved by the ethical committee of the Fourth Military Medical University. The experiments with human subjects were approved by the ethical committee of the Fourth Military Medical University and were carried out with the full, informed consent of the subjects. Funding Information: M.-j.S., K.J., and C.-y.W. contributed equally to this work. The authors thank S.Z. for assistance in the molecular dynamic simulations. This work was supported by grants 81722015, 81870805, 81870787,?and 81720108011?from National Natural Science Foundation of China, grant 2020TD-033?from the Shaanxi Key Scientific and Technological Innovation Team, the Youth Innovation Team of Shaanxi Universities and by grant 2021JC-34 from Distinguished Young Scientists Foundation of Shaanxi Province. H.E. was funded by a Polish Honorable Alexander von Humboldt Fellowship (FNP, Poland) as well as MAESTRO Project (NCN, Poland). All animal experiments were approved by the ethical committee of the Fourth Military Medical University. The experiments with human subjects were approved by the ethical committee of the Fourth Military Medical University and were carried out with the full, informed consent of the subjects. Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Science published by Wiley-VCH GmbH",
year = "2022",
month = feb,
day = "14",
doi = "10.1002/advs.202103693",
language = "English (US)",
volume = "9",
journal = "Advanced Science",
issn = "2198-3844",
publisher = "Wiley-VCH Verlag",
number = "5",
}