Inorganic pyrophosphate as a regulator of hydroxyapatite or calcium pyrophosphate dihydrate mineral deposition by matrix vesicles

Objective: Pathological mineralization is induced by unbalance between pro- and anti-mineralization factors. In calcifying osteoarthritic joints, articular chondrocytes undergo terminal differentiation similar to that in growth plate cartilage and release matrix vesicles (MVs) responsible for hydroxyapatite (HA) or calcium pyrophosphate dihydrate (CPPD) deposition. Inorganic pyrophosphate (PP) is a likely source of inorganic phosphate (Pi) to sustain HA formation when hydrolyzed but also a potent inhibitor preventing apatite mineral deposition and growth. Moreover, an excess of PPi can lead to CPPD formation, a marker of pathological calcification in osteoarthritic joints. It was suggested that the P-i/PPi ratio during biomineralization is a turning point between physiological and pathological mineralization. The aim of this work was to determine the conditions favoring either HA or CPPD formation initiated by MVs. Methods: MVs were isolated from 17-day-old chicken embryo growth plate cartilages and subjected to mineralization in the presence of various P-i/PPi ratios. The mineralization kinetics and the chemical composition of minerals were determined, respectively, by light scattering and infrared spectroscopy. Results: The formation of HA is optimal when the P-i/PPi molar ratio is above 140, but is completely inhibited when the ratio decreases below 70. The retardation of any mineral formation is maximal at P PPi ratio around 30. CPPD is exclusively produced by MVs when the ratio is below 6, but it is inhibited for the ratio exceeding 25. Conclusions: Our findings are consistent with the P-i/PPi ratio being a determinant factor leading to pathological mineralization or its inhibition. (c) 2008 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.