Abstract
In a previous experimental study using a chronic renal failure rat model, a dose-related multiphasic effect of strontium (Sr) on bone formation was found that could be reproduced in an in vitro set-up using primary rat osteoblasts. The results from the latter study allowed us to distinguish between a reduced nodule formation in the presence of an intact mineralization at low Sr-doses (1 Μg/ml) and an interference of the element with the hydroxyapatite (HA) formation at high doses (20–100 Μg/ml). To further investigate the latter effect of Sr on physicochemical bone mineral properties, an in vitro study was set up in which the UMR-106 rat osteosarcoma cell line was exposed to Sr, added to the cell culture medium in a concentration range varying between 0–100 Μg/ml. Temporal growth and functionality of the culture was investigated by measurement of the alkaline phosphatase activity and calcium (Ca) concentration in the culture medium (used as an index of Ca-incorporation, i.e., HA formation) at various time points. At the end of the culture period (14 days post-confluence), samples of the mineralized cultures were taken for further analysis using X-ray diffraction (XRD) and Fourier Transform Infra-Red Spectroscopy (FTIR). Synthetic HA doped with various Sr concentrations (based on the cell culture and previous experimental studies and yielding Sr/(Sr+Ca) ratios ranging from 0–60%), was prepared and examined for crystal growth and solubility. Crystal size was assessed using scanning electron microscopy (SEM). Ca incorporation indicated a reduced mineralization in the 20 and 100 Μg/ml Sr groups vs. controls. Sr-doped synthetic HA showed a significant dose-dependent reduction in crystal growth, as assessed by SEM, and an increase in solubility, apparent from 12.7% Sr/(Sr+Ca) on. Moreover, in both mineralized cultures and synthetic HA, XRD and FTIR analysis showed a reduced crystallinity and altered crystal lattice at similar concentrations. These new data support our previous in vivo and in vitro findings and point to a potential physicochemical interference of Sr with HA formation and crystal properties in vivo.
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Acknowledgments
We acknowledge the European Synchrotron Radiation Facility for provision of synchrotron radiation facilities and we would like to thank Michael Drakopoulos and Andrea Somogyi for assistance in using beamline ID18F. P. Cool acknowledges the FWO-Vlaanderen (Fund for Scientific Research Flanders) for financial support.
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Verberckmoes, S.C., Behets, G.J., Oste, L. et al. Effects of Strontium on the Physicochemical Characteristics of Hydroxyapatite. Calcif Tissue Int 75, 405–415 (2004). https://doi.org/10.1007/s00223-004-0260-4
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DOI: https://doi.org/10.1007/s00223-004-0260-4