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Kinetics of Calcium Oxalate Crystal Growth in the Presence of Osteopontin Isoforms: An Analysis by Scanning Confocal Interference Microcopy

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Abstract

Proteins that inhibit the growth and aggregation of calcium oxalate crystals play important roles in the prevention of kidney stone disease. One such protein is osteopontin (OPN), which inhibits the formation of calcium oxalate monohydrate (COM) in a phosphorylation-dependent manner. To determine the role of phosphate groups in the inhibition of COM growth by OPN, we used scanning confocal interference microscopy to compare the effects of highly phosphorylated OPN from cow milk, less phosphorylated OPN from rat bone, and nonphosphorylated recombinant OPN. COM growth was measured in the principal crystallographic directions <001>, <010>, and <100>, representing lattice-ion addition to {121}, {010}, and {100} faces, respectively. While the shapes of growth curves were very consistent from crystal to crystal, absolute growth rates varied widely. To control for this, results were expressed as changes in the aspect ratios <010>/<001> and <100>/<001>. Compared to control, bone OPN increased <010>/<001> and had no effect on <100>/<001>; milk OPN had no effect on <010>/<001>and decreased <100>/<001>; recombinant OPN had no significant effect on either aspect ratio. These findings indicate that milk OPN interacts with COM crystal faces in order of preference {100} > {121} ≈ {010}, whereas bone OPN interacts in order of preference {100}≈{121} > {010}. As {100} is the most Ca2+-rich face of COM, while {010} is the least Ca2+-rich, it appears that the OPN-mediated inhibition of COM growth occurs through a nonspecific electrostatic interaction between Ca2+ ions of the crystal and phosphate groups of the protein.

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Notes

  1. The convention used for indexing the faces of COM is that of Tazzoli and Domenghetti [26].

  2. The Miller indices used by these authors have been converted to those used in the present study.

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Acknowledgement

The skilled technical assistance of Kari Ann Orlay and Honghong Chen is gratefully acknowledged. The images shown in Fig. 5 were generated by Jason O’Young. This study was supported by the Canadian Institutes of Health Research. A. L. was the recipient of a Studentship in Musculoskeletal Research from the Institute of Musculoskeletal Health and Arthritis.

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Authors and Affiliations

  1. CIHR Group in Skeletal Development and Remodeling, University of Western Ontario, London, ON, Canada

    Aaron Langdon, Bernd Grohe, Harvey A. Goldberg & Graeme K. Hunter

  2. School of Dentistry, University of Western Ontario, London, ON, N6A 5C1, Canada

    Aaron Langdon, Bernd Grohe, Harvey A. Goldberg & Graeme K. Hunter

  3. Department of Biochemistry, University of Western Ontario, London, ON, Canada

    Aaron Langdon, Harvey A. Goldberg & Graeme K. Hunter

  4. Department of Surgery, University of Western Ontario, London, ON, Canada

    Geoffrey R. Wignall & John Denstedt

  5. Department of Anatomy and Cell Biology, University of Western Ontario, London, ON, Canada

    Kem Rogers

  6. Department of Molecular Biology, University of Aarhus, Aarhus, Denmark

    Esben S. Sørensen

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  1. Aaron Langdon
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Correspondence to Graeme K. Hunter.

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Langdon, A., Wignall, G.R., Rogers, K. et al. Kinetics of Calcium Oxalate Crystal Growth in the Presence of Osteopontin Isoforms: An Analysis by Scanning Confocal Interference Microcopy. Calcif Tissue Int 84, 240–248 (2009). https://doi.org/10.1007/s00223-008-9215-5

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