title: Modulation of the initial mineralization process of SaOS-2 cells by carbonic anhydrase activators and polyphosphate.
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.
authors.affiliation: 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, wang013@uni-mainz.de.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Heinz C
authors.initials: HC
authors.lastname: Schröder
authors.forename: Ute
authors.initials: U
authors.lastname: Schlossmacher
authors.forename: Meik
authors.initials: M
authors.lastname: Neufurth
authors.forename: Qingling
authors.initials: Q
authors.lastname: Feng
authors.forename: Bärbel
authors.initials: B
authors.lastname: Diehl-Seifert
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D002119:Calcium Carbonate / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002457:Cell Extracts / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010012:Osteogenesis / Q000502:physiology*; D011122:Polyphosphates / Q000378:metabolism*; D013052:Spectrometry, X-Ray Emission; D047233:Suberites / Q000737:chemistry / Q000502:physiology*
chemical_list: D002457:Cell Extracts; D011122:Polyphosphates; D002256:Carbonic Anhydrases; D002119:Calcium Carbonate