An Ion-Exchange Mechanism of Cartilage Calcification

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Abstract
The provisional calcification of epiphyseal cartilage involves deposition of hydroxyapatite (calcium phosphate) crystals in an extracellular matrix consisting principally of Type II collagen and cartilage proteoglycan. A mechanism is now proposed to explain how epiphyseal cartilage calcification is initiated. Calcium exists at high concentration in cartilage, but is mainly bound to the anionic groups of proteoglycans, and thus is unavailable for precipitation. A local increase in phosphate concentration displaces calcium ions from proteoglycan by an ion-exchange effect, raising the Ca x PO4 product above the threshold for precipitation of hydroxyapatite. Evidence for this hypothesis has been derived from studies of the effect of phosphate on the binding of calcium to cartilage proteoglycan, and on hydroxyapatite formation in the presence of chondroitin sulfate.