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.

Matrix is everywhere: extracellular DNA is a link between biofilm and mineralization in Bacillus cereus planktonic lifestyle

“…refs. 14 and 38 ) together with our observation that exogenous DNA is capable of inducing precipitation in cell-free medium would suggest the direct involvement of the negatively charged eDNA molecules in Ca 2+ recruitment and precipitation. At the same time, the contribution of microenvironment in ECM as well as involvement of amyloids in nucleation cannot be ruled out.…”

“…Besides the role in formation of the protein component of ECM, glyceraldehyde-3-phosphate dehydrogenase has been shown to act as a regulator of biofilm formation in a representative of B. cereus by triggering the formation of extracellular DNA 38 . In the calcium- and urea-free medium B4 , we observed eDNA in relatively small quantities and only at the later stages of the growth.…”

Robust and Scalable In Vitro Surface Mineralization of Inert Polymers with a Rationally Designed Molecular Bridge

“…In addition to organic materials, using this method gives biological organisms (e.g., cells and virus) a mineralization layer to make them have higher viability than native ones in a lot of hostile conditions, including longtime exposure to salt water, elevated temperature, ultraviolet light, lyticase, and osmotic pressure. ,− For instance, periplasmic carbonic-anhydrases contribute to the biomineralization of nanofibrous calcium carbonate in the stalks of Didymosphenia geminate for better stability in various hydrodynamic conditions; extracellular polysaccharides in Chlorella and Scytonema exhibit templating activity toward hydrozincite biomineralization to prevent cell entombment . Although sometimes extracellular macromolecules may cause ectopic mineralization in body tissues, the mechanism is still inspiring for fabricating useful inorganic–organic hybrid materials . By mimicking the biomineralization processes in organisms that can survive in various environments, artificial composite materials can be developed for use in the extremes of modern industries .…”

“…43 Although sometimes extracellular macromolecules may cause ectopic mineralization in body tissues, the mechanism is still inspiring for fabricating useful inorganic−organic hybrid materials. 44 By mimicking the biomineralization processes in organisms that can survive in various environments, artificial composite materials can be developed for use in the extremes of modern industries. 45 The key to engineering molecular bridges is to gather functional groups that provide strong anchors to glue organic materials and reliable sites for the immobilization and growth of inorganic species.…”

Role of Phosphorus-Containing Molecules on the Formation of Nano-Sized Calcium Phosphate for Bone Therapy

“…It should be noted that the metastable ACP phase can be stabilized well in aqueous solution using appropriate additives ( Manuel Delgado-Lopez et al, 2017 ; Mao et al, 2021 ; Ruiz-Agudo et al, 2021 ) and/or ions ( Ding et al, 2014 ). There are numerous excellent previous studies focusing on the regulation of calcium phosphate with various morphologies, such as by adding polymers ( Yao et al, 2019 ), citric acid ( von Schirnding et al, 2021 ), oleic acid ( Li et al, 2017 ), and nucleic acid ( Shen et al, 2021 ). It has been demonstrated that the formation of calcium phosphate can be influenced by the polarity, molecular weight, and electric groups of polymers ( Schweizer and Taubert, 2007 ).…”