Inhibition of in vitro mineralization by aluminum in a clonal osteoblastlike cell line, MC3T3-E1.

Abstract

The direct effect of aluminum on mineralization was examined using an osteoblastlike cell line, MC3T3-E1. The mineralization process was quantitated by measuring 45Ca accumulation into the cell and matrix layer of MC3T3-E1 cells in culture. The accumulation of 45Ca into the cell and matrix layer increased dramatically after 13 days of culture without a parallel change in the DNA content of these cells. Because nodular clusters of cells appear around the same period in which a massive mineralization occurs, the marked increase in 45Ca accumulation after the 13th day of culture appears to represent deposition of 45Ca into the extracellular matrix. Thus, this culture system offers a useful model for making a quantitative estimation of osteoblast-mediated mineralization in vitro. When aluminum was added to this system, the accumulation of 45Ca into the cell matrix layer was inhibited in a dose-dependent manner: 10(-6) M aluminum reduced 45Ca accumulation to 40.8 +/- 2.7% of that in nontreated cells without affecting alkaline phosphatase activity or the DNA content of these cells. Because the concentration of aluminum used in this study is well within the range of serum aluminum levels seen in chronic dialysis patients, the direct effects of aluminum on osteoblast-mediated mineralization shown in the present study may underlie the development of so-called aluminum-induced "osteomalacia" in certain dialysis patients.