Journal
BIOMATERIALS
Volume 34, Issue 34, Pages 8671-8680Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.07.096
Keywords
Bone metabolism; Carbonic anhydrase; Osteoblasts; SaOS-2 cells; Ca-carbonate; Hydroxyapatite
Funding
- ERC Advanced Investigator Grant [268476 BIOSILICA]
- Deutsche Forschungsgemeinschaft [Schr 277/10-2]
- European Commission [604036, 286059, 268476, 311848]
- International Human Frontier Science Program
- Public Welfare Project of Ministry of Land and Resources of the People's Republic of China [201011005-06]
- International Science & Technology Cooperation Program of China [2008DFA00980]
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Ca-phosphate/hydroxyapatite crystals constitute the mineralic matrix of vertebrate bones, while Ca-carbonate dominates the inorganic matrix of otoliths. In addition, Ca-carbonate has been identified in lower percentage in apatite crystals. By using the human osteogenic SaOS-2 cells it could be shown that after exposure of the cells to Ca-bicarbonate in vitro, at concentrations between 1 and 10 mm, a significant increase of Ca-deposit formation results. The crystallite nodules formed on the surfaces of SaOS-2 cells become denser and larger in the presence of bicarbonate if simultaneously added together with the mineralization activation cocktail (beta-glycerophosphate/ascorbic acid/dexamethasone). In parallel, with the increase of Ca-deposit formation, the expression of the carbonic anhydrase-II (CA-II) gene becomes upregulated. This effect, measured on transcriptional level is also substantiated by immunohistological studies. The stimulatory effect of bicarbonate on Ca-deposit formation is prevented if the carbonic anhydrase inhibitor acetazolamide is added to the cultures. Mapping the surface of the Ca-deposit producing SaOS-2 cells by scanning electron microscopy coupled with energy-dispersive X-ray analysis revealed an accumulation of the signals for the element carbon and, as expected, also for phosphorus. Finally, it is shown that ortho-phosphate and hydrolysis products of polyphosphate inhibit CA-II activity, suggesting a feedback regulatory system between the CA-driven Ca-carbonate deposition and a subsequent inactivation of this process by ortho-phosphate. Based on the presented data we suggest that Ca-carbonate deposits act as bioseeds for a downstream Ca-phosphate deposition process. We propose that activators for CA, especially for CA-II, might be beneficial for the treatment of bone deficiency diseases. (C) 2013 Elsevier Ltd. All rights reserved.
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