Mechanism of Calcification: Inhibitory Role of Pyrophosphate

Abstract

THE mechanism of calcification has been considerably clarified recently¹. Collagen fibrils were shown to possess in vitro the property of nucleating hydroxyapatite precipitation and of triggering mineralization^1–3. But why does only part of the collagen present in the organism calcify ? Recently, we suggested that the activating sites of collagen and crystal growth could be blocked in the organism by a plasma inhibitor⁴. Indeed we showed plasma to contain one or several substances highly inhibitory to apatite precipitation. The technique used was to determine in vitro, at physiological conditions, the minimum ion product (Ca) × (P) necessary for hydroxyapatite precipitation. After addition of plasma, the rise of this minimum product revealed the presence of inhibitors. As the inhibitor was shown to be destroyed by alkaline phosphatase, and the polyphosphates to have a strong inhibitory activity at concentrations as low as 10⁻⁷ M, we suggested this inhibitor to be a polyphosphate. However, to our knowledge, no such compound has so far been demonstrated in plasma or in urine.