title: Amorphous Ca²⁺ polyphosphate nanoparticles regulate the ATP level in bone-like SaOS-2 cells.
abstract: Polyphosphate (polyP) is a physiologically occurring polyanion that is synthesized especially in bone-forming osteoblast cells and blood platelets. We used amorphous polyP nanoparticles, complexed with Ca(2+), that have a globular size of ∼100 nm. Because polyP comprises inorganic orthophosphate units that are linked together through high-energy phosphoanhydride bonds, we questioned whether the observed morphogenetic effect, elicited by polyP, is correlated with the energy-generating machinery within the cells. We show that exposure of SaOS-2 osteoblast-like cells to polyP results in a strong accumulation of mitochondria and a parallel translocation of the polyP-degrading enzyme alkaline phosphatase to the cell surface. If SaOS-2 cells are activated by the mineralization activation cocktail (comprising β-glycerophosphate, ascorbic acid and dexamethasone) and additionally incubated with polyP, a tenfold intracellular increase of the ATP level occurs. Even more, in those cells, an intensified release of ATP into the extracellular space is also seen. We propose and conclude that polyP acts as metabolic fuel after the hydrolytic cleavage of the phosphoanhydride linkages, which contributes to hydroxyapatite formation on the plasma membranes of osteoblasts.
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany wmueller@uni-mainz.de wang013@uni-mainz.de.
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany Biomaterials Department, Inorganic Chemical Industries Division, National Research Center, Doki 11884, Cairo, Egypt.
authors.forename: Emad
authors.initials: E
authors.lastname: Tolba
authors.affiliation: Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Feng
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Markl
authors.affiliation: Department of Zoology, Johannes Gutenberg-University, Johannes-von-Müller-Weg 6, D-55099 Mainz, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Kokkinopoulou
authors.affiliation: ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany wmueller@uni-mainz.de wang013@uni-mainz.de.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D005994:Glycerophosphates / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism; D011122:Polyphosphates / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D000469:Alkaline Phosphatase; D002118:Calcium; D005994:Glycerophosphates; D000071228:Polyelectrolytes; D011108:Polymers; D011122:Polyphosphates; C031463:beta-glycerophosphoric acid
keywords: ATP level; Bone formation; Polyphosphate; Regenerative medicine; SaOS-2 cells; Tissue engineering