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Modulation of the Initial Mineralization Process of SaOS-2 Cells by Carbonic Anhydrase Activators and Polyphosphate

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Abstract

Ca-phosphate/hydroxyapatite (HA) crystals constitute the mineral matrix of vertebrate bones, while Ca-carbonate is the predominant mineral of many invertebrates, like mollusks. Recent results suggest that CaCO3 is also synthesized during early bone formation. We demonstrate that carbonic anhydrase-driven CaCO3 formation in vitro is activated by organic extracts from the demosponge Suberites domuncula as well as by quinolinic acid, one component isolated from these extracts. Further results revealed that the stimulatory effect of bicarbonate (HCO3 −) ions on mineralization of osteoblast-like SaOS-2 cells is strongly enhanced if the cells are exposed to inorganic polyphosphate (polyP), a linear polymer of phosphate linked by energy-rich phosphodiester bonds. The effect of polyP, administered as polyP (Ca2+ salt), on HA formation was found to be amplified by addition of the carbonic anhydrase-activating sponge extract or quinolinic acid. Our results support the assumption that CaCO3 deposits, acting as bio-seeds for Ca-carbonated phosphate formation, are formed as an intermediate during HA mineralization and that the carbonic anhydrase-mediated formation of those deposits is under a positive–negative feedback control by bone alkaline phosphatase-dependent polyP metabolism, offering new targets for therapy of bone diseases/defects.

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Acknowledgments

W. E. G. M. is a holder of an ERC Advanced Investigator Grant (268476 BIOSILICA). This work was supported by grants from the Deutsche Forschungsgemeinschaft (Schr 277/10-3), the European Commission (“Bio-Scaffolds-Customized Rapid Prototyping of Bioactive Scaffolds,” 604036; Industry-Academia Partnerships and Pathways “CoreShell,” 286059; “MarBioTec*EU-CN*,” 268476; and “BlueGenics,” 311848), and the International Human Frontier Science Program.

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  1. ERC Advanced Investigator Grant Research Group at Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, Duesbergweg 6, 55128, Mainz, Germany

    Xiaohong Wang, Heinz C. Schröder, Ute Schlossmacher, Meik Neufurth & Werner E. G. Müller

  2. Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing, 100084, China

    Qingling Feng

  3. NanotecMARIN, Duesbergweg 6, 55128, Mainz, Germany

    Bärbel Diehl-Seifert

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  1. Xiaohong Wang
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Correspondence to Xiaohong Wang or Werner E. G. Müller.

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Wang, X., Schröder, H.C., Schlossmacher, U. et al. Modulation of the Initial Mineralization Process of SaOS-2 Cells by Carbonic Anhydrase Activators and Polyphosphate. Calcif Tissue Int 94, 495–509 (2014). https://doi.org/10.1007/s00223-013-9833-4

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