Differential effects of zinc and magnesium ions on mineralization activity of phosphatidylserine calcium phosphate complexes

Mg2+ and Zn2+ are present in the mineral of matrix vesicles (MVs) and biological apatites, and are known to influence the onset and progression of mineral formation by amorphous calcium phosphate (ACP) and hydroxyapatite (HAP). However, neither has been studied systematically for its effect on mineral formation by phosphatidylserine–Ca2+–Pi complexes (PS–CPLX), an important constituent of the MV nucleation core. Presented here are studies on the effects of increasing levels of Mg2+ and Zn2+ on the process of mineral formation, either when present in synthetic cartilage lymph (SCL), or when incorporated during the formation of PS–CPLX. Pure HAP and PS–CPLX proved to be powerful nucleators, but ACP took much longer to induce mineral formation. In SCL, Mg2+ and Zn2+ had significantly different inhibitory effects on the onset and amount of mineral formation; HAP and PS–CPLX were less affected than ACP. Mg2+ and Zn2+ caused similar reductions in the rate and length of rapid mineral formation, but Zn2+ was a more potent inhibitor on a molar basis. When incorporated into PS–CPLX, Mg2+ and Zn2+ caused significantly different effects than when present in SCL. Even low, subphysiological levels of Mg2+ altered the inherent structure of PS–CPLX and markedly reduced its ability to induce and propagate mineral formation. Incorporated Zn2+ caused significantly less effect, low (<20 μM) levels causing almost no inhibition. Levels of Zn2+ present in MVs do not appear to inhibit their nucleational activity.