Influence of trace metal ions on matrix vesicle calcification

Abstract

Since the proposal by Roivison that alkaline phosphatase (ALP) has a role in calcification [ 11, and the later demonstration that its activity was dependent on the presence of Zn2” [2], a role for trace metals in biological mineralization has been indicated. Nutritional studies in poultry in the 1950’s and 60’s showed that dietary deficiencies of Mn2+, Cu2+, or Zn*+ resulted in severe skeletal disorders [3]. Subsequently, it was found that excessive amounts of these metal ions could a!so be harmful to the skeletal system. In vitro studies indicated an inhibitory effect of metal ions on endochondral mineralization [4]. In more recent years, toxic metal ions such as Cd2+ and A13+ have been identified as etiological agents in a number of bone diseases [S-6]. Prior to the discovery of matrix vesicles (MV) by Anderson [7] and Bonucci [8], histochemical studies showed a colocalization of Zn2+ and Sudanophilic material in the hypertrophic region of the epiphyseal growth plate [9]. The discovery of MV readily explained the Sudanophilic reaction, however, it has been only recently that these structures were found to contain substantial amounts of Zn2+ [lo]. Since our discovery of the importance of Zn*+ in MV mineralization, we have investigated a number of aspects of MV function which may be affected by the presence of trace metal ions, including: 1) MV enzyme activities; 2) mineral ion transport; and 3) mineral nucleation, maturation, and growth.