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

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Extracellular DNA: A Missing Link in the Pathogenesis of Ectopic Mineralization
Advanced Science ( IF 14.3 ) Pub Date : 2021-12-23 , DOI: 10.1002/advs.202103693
Min-Juan Shen ₁ , Kai Jiao ₁ , Chen-Yu Wang ₁ , Hermann Ehrlich _{2,

3} , Mei-Chen Wan ₁ , Dong-Xiao Hao _{1,

4} , Jing Li ₁ , Qian-Qian Wan ₁ , Lige Tonggu ₅ , Jian-Fei Yan ₁ , Kai-Yan Wang ₁ , Yu-Xuan Ma ₁ , Ji-Hua Chen ₁ , Franklin R Tay ₆ , Li-Na Niu ₁

Affiliation

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.

中文翻译：

细胞外 DNA：异位矿化发病机制中的缺失环节

尽管脱氧核糖核酸 (DNA) 是生命本质的遗传编码，但这些大分子或其成分在细胞死亡后不一定会丢失。细胞外 DNA 和生物矿化之间似乎存在联系。在这里，作者证明了细胞外 DNA 作为胶原纤维内矿化的引发剂。体外和体内生物矿化模型证实了这一点。由于它们的聚阴离子特性，细胞外 DNA 分子能够稳定过饱和磷酸钙溶液并在 24 小时内完全矿化 2D 和 3D 胶原基质。细胞外 DNA 在胶原蛋白生物矿化中的有效性归因于通过氢键将 DNA 吸引到胶原原纤维上引发的相对稳定的无定形液滴形成。这些发现表明，细胞外DNA对于制造用于组织工程的无机-有机杂化材料具有仿生意义。DNA 诱导的胶原纤维内矿化为不同身体组织中异位矿化的发病机制提供了线索。使用 DNase 在特定组织部位靶向细胞外 DNA 为治疗与异位矿化相关的疾病提供了潜在的解决方案。这些发现表明，细胞外DNA对于制造用于组织工程的无机-有机杂化材料具有仿生意义。DNA 诱导的胶原纤维内矿化为不同身体组织中异位矿化的发病机制提供了线索。使用 DNase 在特定组织部位靶向细胞外 DNA 为治疗与异位矿化相关的疾病提供了潜在的解决方案。这些发现表明，细胞外DNA对于制造用于组织工程的无机-有机杂化材料具有仿生意义。DNA 诱导的胶原纤维内矿化为不同身体组织中异位矿化的发病机制提供了线索。使用 DNase 在特定组织部位靶向细胞外 DNA 为治疗与异位矿化相关的疾病提供了潜在的解决方案。

更新日期：2021-12-23

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