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Citrate Occurs Widely in Healthy and Pathological Apatitic Biomineral: Mineralized Articular Cartilage, and Intimal Atherosclerotic Plaque and Apatitic Kidney Stones

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Abstract

There is continuing debate about whether abundant citrate plays an active role in biomineralization of bone. Using solid state NMR dipolar dephasing, we examined another normally mineralized hard tissue, mineralized articular cartilage, as well as biocalcifications arising in pathological conditions, mineralized intimal atherosclerotic vascular plaque, and apatitic uroliths (urinary stones). Residual nondephasing 13C NMR signal at 76 ppm in the spectra of mineralized cartilage and vascular plaque indicates that a quaternary carbon atom resonates at this frequency, consistent with the presence of citrate. The presence, and as yet unproven possible mechanistic involvement, of citrate in tissue mineralization extends the compositional, structural, biogenetic, and cytological similarities between these tissues and bone itself. Out of 10 apatitic kidney stones, five contained NMR-detectable citrate. Finding citrate in a high proportion of uroliths may be significant in view of the use of citrate in urolithiasis therapy and prophylaxis. Citrate may be essential for normal biomineralization (e.g., of cartilage), play a modulatory role in vascular calcification which could be a target for therapeutic intervention, and drive the formation of apatitic rather than other calcific uroliths, including more therapeutically intractable forms of calcium phosphate.

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Acknowledgments

The U.K. Biotechnology and Biological Sciences Research Council (BBSRC), the British Heart Foundation (BHF), the South African National Research Foundation (NRF) and Medical Research Council (MRC), and the U.K. Royal Society of Chemistry for a SA/UK Science Networks Grant.

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Authors and Affiliations

  1. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK

    David G. Reid & Melinda J. Duer

  2. Department of Chemistry, University of Cape Town, Rondebosch, 7700, South Africa

    Graham E. Jackson & Allen L. Rodgers

  3. Centre for Equine Studies, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK

    Rachel C. Murray

  4. BHF Centre of Research Excellence, Cardiovascular Division, James Black Centre, King’s College London, 125 Coldharbour Lane, London, SE5 9NU, UK

    Catherine M. Shanahan

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  1. David G. Reid
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  2. Melinda J. Duer
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Correspondence to Melinda J. Duer.

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Reid, D.G., Duer, M.J., Jackson, G.E. et al. Citrate Occurs Widely in Healthy and Pathological Apatitic Biomineral: Mineralized Articular Cartilage, and Intimal Atherosclerotic Plaque and Apatitic Kidney Stones. Calcif Tissue Int 93, 253–260 (2013). https://doi.org/10.1007/s00223-013-9751-5

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  • DOI: https://doi.org/10.1007/s00223-013-9751-5

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