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Mineralization of bone‐related Sa OS ‐2 cells under physiological hypoxic conditions
Author(s) -
Müller Werner E. G.,
Schröder Heinz C.,
Tolba Emad,
DiehlSeifert Bärbel,
Wang Xiaohong
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13552
Subject(s) - chemistry , carbonic anhydrase , mineralization (soil science) , alkaline phosphatase , bicarbonate , glycolysis , polyphosphate , oxygen tension , hypoxia (environmental) , mesenchymal stem cell , biophysics , osteoblast , oxygen , biochemistry , anaerobic glycolysis , microbiology and biotechnology , in vitro , metabolism , enzyme , biology , phosphate , organic chemistry , nitrogen
Inorganic polyphosphate (polyP) is a physiological energy‐rich polymer with multiple phosphoric anhydride bonds. In cells such as bone‐forming osteoblasts, glycolysis is the main pathway generating metabolic energy in the form of ATP . In the present study, we show that, under hypoxic culture conditions, the growth/viability of osteoblast‐like Sa OS ‐2 cells is not impaired. The addition of polyP to those cells, administered as amorphous calcium polyP nanoparticles ( aC a‐polyP‐ NP ; approximate size 100 nm), significantly increased the proliferation of the cells. In the presence of polyP, the cells produce significant levels of lactate, the end product of anaerobic glycolysis. Under those conditions, an eight‐fold increase in the steady‐state level of the membrane‐associated carbonic anhydrase IX is found, as well as a six‐fold induction of the hypoxia‐inducible factor 1. Consequently, biomineral formation onto the Sa OS ‐2 cells decreases under low oxygen tension. If the polyP nanoparticles are added to the cells, the degree of mineralization is enhanced. These changes had been measured also in human mesenchymal stem cells. The assumption that the bicarbonate, generated by the carbonic anhydrase in the presence of polyP under low oxygen, is deposited as a constituent of the bioseeds formed during initial hydroxyapatite formation is corroborated by the identification of carbon besides of calcium, oxygen and phosphorus in the initial biomineral deposit onto the cells using the sensitive technology of high‐resolution energy dispersive spectrometry mapping. Based on these data, we conclude that polyP is required for the supply of metabolic energy during bone mineral formation under physiological, hypoxic conditions, acting as a ‘metabolic fuel’ for the cells to grow.