Citrate regulates extracellular matrix mineralization during osteoblast differentiation in vitro.

The extremely high levels of citrate in bone highlight its important role, which must be involved in some essential functional or structural role that is required for the development and maintenance of normal bone. However, biomineralization researches have emphasized the interaction between the citrate and inorganic minerals during crystallization in cell-free systems. It is difficult to obtain a thorough and comprehensive understanding from cell-free experimental conditions and treatment methods. In this study, by proposing an osteoblast mineralization experimental model, we explored the regulation of citrate on bone apatite crystal structure. Our studies show that citrate stabilizes two precursors and then inhibits their transformation into hydroxyapatite. Concomitantly, the smaller size and lower crystallinity mineral deposition emerge during citrate-mediated osteogenic mineralization. These findings may provide a new perspective for the mechanism of osteogenic mineralization and a basis for further understanding of bone metabolism.