TY - JOUR
T1 - Citrate occurs widely in healthy and pathological apatitic biomineral
T2 - Mineralized articular cartilage, and intimal atherosclerotic plaque and apatitic kidney stones
AU - Reid, David G.
AU - Duer, Melinda J.
AU - Jackson, Graham E.
AU - Murray, Rachel C.
AU - Rodgers, Allen L.
AU - Shanahan, Catherine M.
PY - 2013/9/1
Y1 - 2013/9/1
N2 - 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.
AB - 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.
KW - Apatite
KW - Atherosclerotic plaque
KW - Biomineralization
KW - Brushite
KW - Mineralized cartilage
KW - Urolithiasis
UR - http://www.scopus.com/inward/record.url?scp=84882455961&partnerID=8YFLogxK
U2 - 10.1007/s00223-013-9751-5
DO - 10.1007/s00223-013-9751-5
M3 - Article
C2 - 23780351
AN - SCOPUS:84882455961
SN - 0171-967X
VL - 93
SP - 253
EP - 260
JO - Calcified Tissue International
JF - Calcified Tissue International
IS - 3
ER -