Summary
Proteoglycans are recognized to inhibit calcium pyrophosphate dihydrate (CPPD) crystal formation but the mechanisms are not known. To study the role of carboxylate (−CO2 −) ligands, the possible inhibitor effects of sodium acetate, sodium D-glucuronate, disodium malate, and trisodium citrate were studied using solution mixtures containing [Ca2+]=1.5 mM, [Mg2+]=0.5 mM, [PPi] =0.1 mM, [Pi]=0.1 mM, [Na+]=140 mM, 37°C, pH 7.4 with or without 9.5±0.5 mg CPPD (seed) crystals. These studies showed that monocarboxylates (acetate, glucuronate) have little inhibitive effect. Progressively greater inhibition was found with dicarboxylate (malate) and tricarboxylate (citrate) indicating that the arrangement of carboxylate (and sulfate) ligands on proteoglycan is more important than the inhibitory effect of individual ligands.
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References
McCarty D (1983) Crystals, joints, and consternation. Annals Rheum Dis 42:243–253
Pritzker KPH (1980) Crystal-associated arthropathies: what's new in old joints? J Am Geriat Soc 28:439–445
Lagier R (1981) L'approche anatomo-pathologique du concept de chondrocalcinose articulaire. Rheum 33:421–437
Mitrovic DR (1983) Pathology of articular deposition of calcium salts and their relationship to osteoarthrosis. Ann Rheum Dis 42:19–23
Renlund RC, Pritzker KPH, Cheng P-T, Kessler MJ (1986) Rhesus monkeys (Macaca mulatta) as a model for calcium pyrophosphate dihydrate crystal deposition disease. J Med Primatol 15:11–16
Pritzker KPH, Cheng P-T, Hunter GK, Grynpas MD, Kessler MJ, Renlund RC (1984) In vitro and in vivo models of calcium pyrophosphate crystal formation. In: Butler WT (ed) The chemistry and biology of mineralized tissues. EBSCO Media, Birmingham, Alabama 381–384
Cheng P-T, Pritzker KPH, Adams ME, Nyburg C, Omar SA (1980) Calcium pyrophosphate crystal formation in aqueous solutions. J Rheumatol 7:609–616
Hearn PR, Russell RGG (1980) Formation of calcium pyrophosphate crystals in vitro: implications for calcium pyrophosphate crystal deposition disease (Pseudogout). Ann Rheum Dis 39:222–227
Cheng P-T, Pritzker KPH (1981) The effect of calcium and magnesium ions on calcium pyrophosphate crystal formation in aqueous solutions. J Rheumatol 8:772–782
Cheng P-T, Pritzker KPH (1983) Pyrophosphate, phosphate ion interaction: effects on calcium pyrophosphate and calcium hydroxyapatite crystal formation in aqueous solutions. J Rheumatol 10:770–777
Pritzker KPH, Cheng P-T, Adams ME, Nyburg SC (1978) Calcium pyrophosphate dihydrate crystal formation in model hydrogels. J Rheumatol 5:469–473
Pritzker KPH, Cheng P-T, Omar SA, Nyburg SC (1981) Calcium pyrophosphate crystal formation in model hydrogels II: hyaline articular cartilage as a gel. J Rheumatol 8:451–455
Harries JE, Dieppe PA, Heap P, Gilgead J, Mather M, Shah JS (1983) In vitro growth of calcium pyrophosphate crystals in polyacrylamide gels. Ann Rheum Dis 42:100
Mandel NS, Mandel GS, Carroll DJ, Halverson PB (1984) Calcium pyrophosphate crystal deposition: an in vitro study using a gelatin matrix model. Arth Rheum 27:789–796
Howell DS, Martel-Pelletier J, Pelletier JP, Morales S, Muniz O (1984) NTP pyrophosphohydrolase in human chondrocalcinotic and osteoarthritic cartilage II: further studies on histologic and subcellular distribution. Arch Rheum 27:193–199
Bjelle AO (1973) The glycosaminoglycans of articular cartilage in calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (chondrocalcinosis articularis or pyrophosphate arthropathy). Calcif Tissue Res 12:37–46
Cheng P-T, Grynpas MD, Pritzker KPH (1984) Ultrastructural and analytical studies of amorphous calcium phosphates, pyrophosphates and phosphate-pyrophosphate complexes (Abstract) Acta Cryst A40:S476
Blumenthal NC, Posner AS, Silverman LD, Rosenberg LC (1979) Effect of proteoglycans on in vitro hydroxyapatite formation. Calcif Tissue Int 27:75–82
Davies CW (1962) Ion association. Butterworth & Co. London
Sillen LG, Martell AE (1971) Stability constants of metal-ion complexes. The Chemical Society, London
Mann S (1981) Mineralization in biological systems. Structure and bonding. Springer-Verlag, Berlin, 54:127–174
Brecevic L, Furedi-Milhofer H (1979) Precipitation of calcium phosphates from electrolyte solutions V: the influence of citrate ions. Calcif Tissue Int 28:131–136
Buckwalter JA (1983) Proteoglycan structure in calcifying cartilage. Clin Orthop Relat Res 172:207–232
Hunter GK, Allen BL, Grynpas MD, Cheng P-T (1985) Inhibition of hydroxyapatite formation in collagen gels by chondroitin sulphate. Biochem J 228:463–469
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Cheng, PT., Pritzker, K.P.H. Inhibition of calcium pyrophosphate dihydrate crystal formation: Effects of carboxylate ions. Calcif Tissue Int 42, 46–52 (1988). https://doi.org/10.1007/BF02555838
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DOI: https://doi.org/10.1007/BF02555838