THE SERUM-PROTEIN ALPHA(2)-HS GLYCOPROTEIN FETUIN INHIBITS APATITE FORMATION IN-VITRO AND IN MINERALIZING CALVARIA CELLS - A POSSIBLE ROLE IN MINERALIZATION AND CALCIUM HOMEOSTASIS/

We present data suggesting a function of alpha(2)-HS glycoproteins/fet uins in serum and in mineralization, namely interference with calcium salt precipitation. Fetuins occur in high serum concentration during f etal life. They accumulate in bones and teeth as a major fraction of n oncollagenous bone proteins, The expression pattern in fetal mice conf irms that fetuin is predominantly made in the liver and is accumulated in the mineralized matrix of bones, We arrived at a hypothesis on the molecular basis of fetuin function in bones using primary rat calvari a osteoblast cultures and salt precipitation assays. Our results indic ate that fetuins inhibit apatite formation both in cell culture and in the test tube, This inhibitory effect is mediated by acidic amino aci ds clustering in cystatin-like domain D1, Fetuins account for roughly half of the capacity of serum to inhibit salt precipitation. We propos e that fetuins inhibit phase separation in serum and modulate apatite formation during mineralization.