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In vitro inhibition of membrane-mediated calcification by novel phosphonates

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Abstract

The effects of a series of novel phosphonates on the kinetics of mineral development in an ionophore-primed 7:2:1 phosphatidylcholine (PC): dicetylphosphate (DCP): cholesterol (Chol) liposomal model system are reported. When present at 2.5 μmol/liter or 25 μmol/liter concentrations in the solution surrounding the liposomes, the investigated phosphonates did not significantly delay the initial formation of hydroxyapatite-like calcium phosphate salts (HAP) within the liposomes or the penetration of HAP crystals through the enclosing membranes. However, the phosphonates variably retarded the subsequent growth and proliferation of the HAP crystals once they became directly exposed to the phosphonate-containing solution. The effectiveness of phosphonates in inhibiting extraliposomal precipitation strongly depended on their structure. The inhibitory action on active surface growth sites of released intraliposomal crystals was found to be the most effective if the phosphonate molecule, contained two phosphonic groups linked to the same C atom. At a phosphonate concentration of 25 μmol/liter, the, following general order of effectiveness was established: geminal bisphosphonate≥geminal tetrakisphosphonate > bisacylphosphonates > monoacyl-phosphonate > bisalkylphosphonate. Within the bisacylphosphonate family, the highest inhibitory action was observed when four of five-CH2-groups separated the ketophosphonic groups.

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Authors and Affiliations

  1. National Institute of Dental Research's Bone Research Branch Associate Program, National Institute of Standards and Technology, 20899, Gaithersburg, Maryland, USA

    D. Skrtic & E. D. Eanes

  2. American Dental Association Health Foundation, Paffenbarger Research Center, National Institute of Standards and Technology, 20899, Gaithersburg, Maryland, USA

    N. Eidelman

  3. Department of Chemistry, Ruder Boskovic Institute, 41000, Zagreb, Croatia

    D. Skrtic

  4. Department of Pharmacy, School of Pharmacy, The Hebrew University of Jerusalem, 91120, Jerusalem, Israel

    G. Golomb

  5. Department of Pharmaceutical Chemistry, School of Pharmacy, The Hebrew University of Jerusalem, 91120, Jerusalem, Israel

    E. Breuer

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  1. D. Skrtic
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  2. N. Eidelman
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  3. G. Golomb
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  4. E. Breuer
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  5. E. D. Eanes
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Additional information

Certain commercial materials and equipment are identified in this paper to specify experimental procedure. In no instances does such identification imply recommendation or endorsement by the National Institute of Standards and Technology or that the material and the equipment identified is necessarily the best available for the purpose.

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Skrtic, D., Eidelman, N., Golomb, G. et al. In vitro inhibition of membrane-mediated calcification by novel phosphonates. Calcif Tissue Int 58, 347–354 (1996). https://doi.org/10.1007/BF02509384

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  • DOI: https://doi.org/10.1007/BF02509384

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